Förderzeitraum 2017
Refine
Has Fulltext
- yes (125)
Is part of the Bibliography
- yes (125)
Document Type
- Journal article (125)
Language
- English (125)
Keywords
- gene expression (5)
- B cells (4)
- Trypanosoma (4)
- fungi (4)
- regulatory T cells (4)
- Candida albicans (3)
- ants (3)
- blood (3)
- ischemic stroke (3)
- social systems (3)
- CXCR4 (2)
- PRRT (2)
- agroecology (2)
- animal sociality (2)
- athletes (2)
- carbon dioxide (2)
- cell cycle and cell division (2)
- cell differentiation (2)
- ceramide (2)
- colorectal cancer (2)
- coronary heart disease (2)
- dendritic cells (2)
- guideline adherence (2)
- humidity (2)
- hyperexpression techniques (2)
- immune evasion (2)
- inflammation (2)
- lung cancer (2)
- messenger RNA (2)
- metabolism (2)
- metastasis (2)
- microRNAs (2)
- molecular medicine (2)
- multiple myeloma (2)
- mutation (2)
- nesting habits (2)
- osteoarthritis (2)
- pediatric (2)
- regulator genes (2)
- small interfering RNAs (2)
- symbiosis (2)
- team sport (2)
- tight junctions (2)
- transcription factors (2)
- validation (2)
- A53T (1)
- ADAMTS (1)
- ALOS (1)
- ALOS-2 (1)
- ALS (1)
- Adrenocortical Carcinoma (1)
- Akutes Nierenversagen (1)
- Alpen (1)
- ApoE\(^{(-/-)}\) (1)
- B cell receptors (1)
- BCI (1)
- BDNF (1)
- BMP (1)
- BMP-2 (1)
- CBF (1)
- CCN2 (1)
- CD28 (1)
- CD28 superagonists (1)
- CD4\(^{+}\) T cells (1)
- CMV (1)
- CTGF (1)
- Ca\(_{v}\)2.2 (1)
- Cell binding (1)
- D665 (1)
- DExD/H-Box RNA helicase (1)
- DNA methylation (1)
- DOTATOC (1)
- EAE (1)
- EEG (1)
- EUROASPIRE survey (1)
- EndoVAC and small bowel (1)
- F-actin (1)
- FTY720 (1)
- Fernerkundung (1)
- GM-CSF (1)
- German translation (1)
- Gletscher (1)
- H441 (1)
- HNSCC (1)
- HeLa cells (1)
- Hoffa (1)
- Hyrtios (1)
- ICD-coding of CKD (1)
- IL-2 (1)
- IMR-90 (1)
- KFZA (1)
- LC-ESI/MS/MS (1)
- LFA-1 (1)
- Langerhans cells (1)
- Lewy-like pathology (1)
- MITE (1)
- MPFL (1)
- MR angiography (1)
- MRI (1)
- Megaponera analis (1)
- N-terminal domain (1)
- NP-hard (1)
- Neisseria (1)
- Neisseria meningitidis (1)
- Osmunda regalis (1)
- P. aeruginosa (1)
- P300 (1)
- PDH (1)
- PER (1)
- PET (1)
- PET/CT (1)
- Parkinson’s disease (1)
- PolSAR (1)
- Positronen-Emissions-Tomografie (1)
- Pycnogenol (1)
- RIG-I (1)
- RNA export (1)
- RNA in situ hybridization (1)
- RNA interference (1)
- RNA-binding proteins (1)
- Radarsat-2 (1)
- RelB (1)
- SAH (1)
- SSTR (1)
- STAT1 (1)
- Salmonellosis (1)
- Shigella (1)
- Shigellosis (1)
- Struktur (1)
- T cell migration (1)
- T cells (1)
- TAB08 (1)
- TGFβ1 (1)
- TGN1412 (1)
- TLO (1)
- TP53 (1)
- Tanzania (1)
- TerraSAR-X (1)
- Tropheryma whipplei (1)
- Trypanosoma brucei (1)
- Tuberculosis (1)
- Tyrian purple (1)
- V. saphena magna (1)
- Whipple's disease (1)
- Wilms tumour (1)
- Yo‐Yo intermittent recovery (1)
- [\(^{68}\)Ga] pentixafor (1)
- [\(^{68}\)Ga]Pentixafor (1)
- accelerometer (1)
- accuracy (1)
- acute (1)
- acute graft-versus-host disease (1)
- adaptation (1)
- adenocarcinoma of the lung (1)
- adhesion (1)
- adhesion molecules (1)
- aerobic glycolysis (1)
- agility (1)
- agomelatine (1)
- agricultural intensity (1)
- airway remodeling (1)
- alkaloids (1)
- altruism (1)
- amyotrophic lateral sclerosis (1)
- anaphylaxis (1)
- anaplasia (1)
- animals (1)
- antibiotics (1)
- antifungals (1)
- antimicrobial resistance (1)
- aortic valve replacement (1)
- apoptosis (1)
- arctic (1)
- assistive technology (1)
- auditory (1)
- autism-like behavior (1)
- autoimmunity (1)
- auxins (1)
- awareness (1)
- bacterial secretion (1)
- bee (1)
- behavior (1)
- bi-compartmental (1)
- bi-compartmental knee arthoplasty (1)
- bioactive (1)
- biofeedback (1)
- biogenic amines (1)
- bioinformatics (1)
- biological pest control (1)
- biological rapid deployment aortic valve (1)
- biomarker (1)
- biophysics (1)
- blood-brain barrier (1)
- bone ligament graft (1)
- brain computer interface (1)
- brain edema (1)
- brain-computer interface (1)
- branch point (1)
- bronchopulmonary dysplasia (1)
- buildup phase (1)
- caffeine (1)
- cancer treatment (1)
- cardiac rehabilitation (1)
- cardiogenic (1)
- cardiogenic shock (1)
- cartilage (1)
- cartographic requirements (1)
- case report (1)
- cell binding (1)
- cell cultures (1)
- cell metabolism (1)
- cell phone conversation (1)
- cell proliferation (1)
- central complex (1)
- ceramide analogs (1)
- change of direction (1)
- change‐of‐direction movement (1)
- characterization (1)
- chemokine receptor (1)
- cholera (1)
- chronic heart failure (1)
- chronic kidney disease (1)
- chronic pain (1)
- circadian rhythm (1)
- clinical applications (1)
- clinical study (1)
- cloning (1)
- co-stimulation, (1)
- coaching (1)
- collagens (1)
- colour (1)
- comparative genomics (1)
- comprehensive management (1)
- coronary artery disease (1)
- correlates (1)
- cortisol (1)
- coverage (1)
- crop (1)
- cross-modal action (1)
- cross-sectional (1)
- cryptic (1)
- curative resection (1)
- cytokine secretion (1)
- cytokines (1)
- decomposition (1)
- deletion mutagenesis (1)
- density functional theory (1)
- derivatives (1)
- desert ants (1)
- desk-based (1)
- diet (1)
- diffusion-weighted MRI (1)
- dislocation (1)
- diurnal profile (1)
- division of labor (1)
- dual polarimetry (1)
- dual tasks (1)
- dual-response costs (1)
- duodenal perforation (1)
- duodenal trauma (1)
- ecological intensification (1)
- ecosystem services (1)
- effort (1)
- ejection fraction (1)
- elderly (1)
- elliptic problems (1)
- encephalitis (1)
- end-user evaluation (1)
- endocrinology (1)
- endophthalmitis (1)
- endothelial cells (1)
- endurance (1)
- epithelial cells (1)
- eukaryota (1)
- euroaspire (1)
- extra corporeal membrane oxygenator (1)
- extracorporeal membrane oxygenation (1)
- factor XII (1)
- fatty degeneration (1)
- fear of progression (1)
- feasibility (1)
- femur (1)
- fetal cord blood (1)
- fetal programming (1)
- fibrinogen (1)
- fibrosis (1)
- fingolimod (1)
- finite differences (1)
- flow cytometry (1)
- foamy viruses (1)
- focal brain lesion (1)
- forager (1)
- foraging (1)
- forest health (1)
- fracture (1)
- fredholm operator (1)
- fullerenes (1)
- fungal genetics (1)
- fungal physiology (1)
- fungal structure (1)
- gambiense (1)
- gastrointestinal tract (1)
- gene regulation (1)
- generation effect (1)
- genetic loci (1)
- genetic variation (1)
- genetically modified plants (1)
- genome sequencing (1)
- genomic damage (1)
- genomic libraries (1)
- genotype (1)
- gestational diabetes mellitus (1)
- glucocorticoids (1)
- glycoprotein receptor Ib (1)
- growth cone (1)
- guideline implementation (1)
- head and neck cancer (1)
- head and neck carcinoma (1)
- health monitoring (1)
- heart failure (1)
- heart valve prosthesis (1)
- height-adjustable desk (1)
- hepatic resection (1)
- herpes virus (1)
- high-volume training (1)
- histones (1)
- hos tcells (1)
- hospital (1)
- human (1)
- hymenoptera (1)
- identification (1)
- immunoblotting (1)
- immunoglobin-A (1)
- immunohistochemistry (1)
- impella 5.0 (1)
- implant (1)
- implant fit (1)
- implant positioning (1)
- implantable neurostimulators (1)
- index analysis (1)
- indigo (1)
- inducible deletion (1)
- infectious-disease diagnostics (1)
- ingestible sensor (1)
- inguinal lymph node dissection (1)
- innate immunity (1)
- insect (1)
- insecticides (1)
- insulin (1)
- insulin treatment (1)
- integer linear programming (1)
- intravenous ceftriaxone (1)
- intravitreal vancomycin and amikacin (1)
- invasion (1)
- ion channels in the nervous system (1)
- juvenile idiopathic arthritis (1)
- kinases (1)
- knee alignment (1)
- knee arthroplasty (1)
- knee osteoarthritis (1)
- laboratory measurements (1)
- laboratory techniques and procedures (1)
- latent change (1)
- learning (1)
- learning outcome (1)
- learning with expository texts (1)
- leaves (1)
- leukemia (1)
- liver resection (1)
- long-term patency (1)
- look-back behavior (1)
- lovastatin (1)
- lung resection (1)
- lymph nodes (1)
- mTOR-inhibitor RAD-001 (1)
- macrophages (1)
- magnetic resonance imaging (1)
- malignant melanoma (1)
- map labeling (1)
- marine natural products (1)
- marine sponges (1)
- maritime pine bark extract (1)
- materials for optics (1)
- mayo stem (1)
- measles (1)
- measurement invariance (1)
- melatonin (1)
- membrane receptor signaling (1)
- memory (1)
- mental health (1)
- meristems (1)
- mice (1)
- microRNA–target interaction (1)
- microsoft band 2 (1)
- microswimmer (1)
- mineralocorticoid antagonist (1)
- minimal invasive surgery (1)
- minimally invasive surgery (1)
- mitochondria (1)
- model organism (1)
- monitoring (1)
- monocytes (1)
- mood states (1)
- motor axon (1)
- motor cortex (1)
- mouse brain microvascular endothelial cell cultur (1)
- mouse model (1)
- mouse models (1)
- multi-leaf collimator (1)
- multi-sensor (1)
- multigrid schemes (1)
- multimedia learning (1)
- multiple sclerosis (1)
- multiple-level replantation (1)
- muscle oxygen saturation (1)
- mushroom body (1)
- myeloid (1)
- nanoscience and technology (1)
- natural approach (1)
- near-infrared spectroscopy (1)
- necrotic cell death (1)
- neisseria meningitidis (1)
- nephroblastoma (1)
- neuroendocrine tumor (1)
- neuronal development (1)
- neutral sphingomyelinase (1)
- none (1)
- numerical analysis (1)
- nurse bee (1)
- occlusion (1)
- occupational sitting and physical activity questionnaire (1)
- octopamine (1)
- ocular infection (1)
- oculomotor control (1)
- office-workers (1)
- older poor readers (1)
- oncostatin M (1)
- opioid peptides (1)
- opioid receptors (1)
- optics and photonics (1)
- oral anticancer drugs (1)
- oral cefpodoxime (1)
- oral doxycycline (1)
- osteopontin (1)
- pH-regulated antigen 1 (Pra1) (1)
- pain (1)
- pain behavior (1)
- parasitic cell cycles (1)
- parasitic diseases (1)
- parasomn (1)
- patella (1)
- pathogens (1)
- patient education (1)
- patient-specific (1)
- patients’ awareness (1)
- peptide receptor (1)
- peptide receptor radionuclide therapy (1)
- performance monitoring (1)
- periodization (1)
- perioperative changes (1)
- pharmacotherapy (1)
- phase contrast (1)
- phenotype (1)
- phosphorylation (1)
- physicians’ awareness (1)
- physiological (1)
- pine bark extract (1)
- planning study (1)
- plant extract (1)
- plant growth and development (1)
- platelets (1)
- pleural mesothelioma (1)
- point mutation (1)
- point-feature label placement (1)
- point-of-care echocardiography (1)
- polarization (1)
- polymers (1)
- polyphenols (1)
- population-based study (1)
- postoperativ (1)
- practical electrodes (1)
- preserved ejection fraction (1)
- prevalence (1)
- primary prevention (1)
- primary school (1)
- prognosis (1)
- proliferation (1)
- prosocial behavior (1)
- prosocial tendency measure (1)
- protein structure (1)
- proteomes (1)
- psychosocial workplace risk assessment (1)
- pulley rupture (1)
- pulse wave velocity (1)
- purine-rich element (1)
- qPCR (1)
- quad polarimetry (1)
- quality indicators (1)
- quality of health care (1)
- quality of life (1)
- radionuclide therapy (1)
- radiotherapy (1)
- random forest (1)
- randomized controlled study (1)
- re-irradiation (1)
- re-planning (1)
- reading comprehension (1)
- recovery (1)
- regional recurrence (1)
- relA (1)
- repeated sprint ability (1)
- rescue behavior (1)
- resolvin (1)
- resveratrol (1)
- retinal development (1)
- retrospective study (1)
- ring-barking (1)
- risk factor (1)
- risk factor control (1)
- robotic table motion (1)
- root growth (1)
- rotator cuff (1)
- sarcoidosis (1)
- scanning electron microscopy (1)
- screening for distress (1)
- secondary brain damage (1)
- sedentary behavior (1)
- self-management (1)
- self-reactivity (1)
- semiconductors (1)
- sensor assessment (1)
- sept3 (1)
- sept5a (1)
- sept5b (1)
- septic (1)
- septin (1)
- sequence assembly tools (1)
- serum (1)
- shape (1)
- shock (1)
- short hip stem (1)
- shoulder surgery (1)
- signaling (1)
- single-electron transistor (1)
- sitting time (1)
- sky-compass pathway (1)
- sleep-related eating (1)
- sleeping sickness (1)
- somatostatin receptors (1)
- specimen storage (1)
- spectroscopy (1)
- speed (1)
- spider (1)
- spidroin (1)
- splice regulation (1)
- sports (1)
- stereotactic irradiation (1)
- stringent response (1)
- stroke register (1)
- stroke unit (1)
- stroke unit care (1)
- structural biology (1)
- study system (1)
- sucrose (1)
- surfactants (1)
- surgery (1)
- surgical oncology (1)
- surgical resection (1)
- surgical site infection (1)
- surveillance (1)
- survival (1)
- survival analysis (1)
- sustained attention (1)
- syllable-based intervention (1)
- synovial fluid (1)
- synovitis (1)
- systems biology (1)
- systolic dysfunction (1)
- task rules (1)
- technology (1)
- tetracyclines (1)
- tetraparesis (1)
- theranostics (1)
- therapeutic strategy (1)
- throat (1)
- thrombo-inflammation (1)
- topic ofloxacin (1)
- total hip arthroplasty (1)
- toxins (1)
- training intensity distribution (1)
- training optimization (1)
- transcriptional control (1)
- transient middle cerebral artery (1)
- transient middle cerebral artery occlusion (1)
- transient receptor potential channels (1)
- transstomal endoluminal vacuum therapy (1)
- trkB (1)
- tsetse fly (1)
- tumour heterogeneity (1)
- tundra (1)
- ultrasound (1)
- vaccination (1)
- variability (1)
- varicella (1)
- vascular surgery (1)
- vector navigation (1)
- vespula (1)
- vigilance (1)
- virtual isocentre (1)
- virulenceregulatory evolution (1)
- visual (1)
- visual orientation (1)
- vitrectomy (1)
- water microbiology (1)
- wearable (1)
- wearable sensors (1)
- weight loss (1)
- word reading fluency (1)
- work-related stress (1)
- yellow fluorescent protein (1)
- α-synuclein (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (23)
- Institut für Klinische Epidemiologie und Biometrie (9)
- Institut für Psychologie (9)
- Abteilung für Molekulare Innere Medizin (in der Medizinischen Klinik und Poliklinik II) (8)
- Institut für Sportwissenschaft (8)
- Institut für Virologie und Immunbiologie (8)
- Neurologische Klinik und Poliklinik (8)
- Klinik und Poliklinik für Thorax-, Herz- u. Thorakale Gefäßchirurgie (7)
- Klinik und Poliklinik für Unfall-, Hand-, Plastische und Wiederherstellungschirurgie (Chirurgische Klinik II) (7)
- Medizinische Klinik und Poliklinik I (7)
Background
40–50% of patients with colorectal cancer (CRC) will develop liver metastases (CRLM) during the course of the disease. One third of these patients will additionally develop pulmonary metastases.
Methods
137 consecutive patients with CRLM, were analyzed regarding survival data, clinical, histological data and treatment. Results were stratified according to the occurrence of pulmonary metastases and metastases resection.
Results
39% of all patients with liver resection due to CRLM developed additional lung metastases. 44% of these patients underwent subsequent pulmonary resection. Patients undergoing pulmonary metastasectomy showed a significantly better five-year survival compared to patients not qualified for curative resection (5-year survival 71.2% vs. 28.0%; p = 0.001). Interestingly, the 5-year survival of these patients was even superior to all patients with CRLM, who did not develop pulmonary metastases (77.5% vs. 63.5%; p = 0.015). Patients, whose pulmonary metastases were not resected, were more likely to redevelop liver metastases (50.0% vs 78.6%; p = 0.034). However, the rate of distant metastases did not differ between both groups (54.5 vs.53.6; p = 0.945).
Conclusion
The occurrence of colorectal lung metastases after curative liver resection does not impact patient survival if pulmonary metastasectomy is feasible. Those patients clearly benefit from repeated resections of the liver and the lung metastases.
C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50% of G2 and 80% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.
Cross-modal Action Complexity: Action- and Rule-related Memory Retrieval in Dual-response Control
(2017)
Normally, we do not act within a single effector system only, but rather coordinate actions across several output modules (cross-modal action). Such cross-modal action demands can vary substantially with respect to their complexity in terms of the number of task-relevant response combinations and to-be-retrieved stimulus-response (S-R) mapping rules. In the present study, we study the impact of these two types of cross-modal action complexity on dual-response costs (i.e., performance differences between single- and dual-action demands). In Experiment 1, we combined a manual and an oculomotor task, each involving four response alternatives. Crucially, one (unconstrained) condition involved all 16 possible combinations of response alternatives, whereas a constrained condition involved only a subset of possible response combinations. The results revealed that preparing for a larger number of response combinations yielded a significant, but moderate increase in dual-response costs. In Experiment 2, we utilized one common lateralized auditory (e.g., left) stimulus to trigger incompatible response compounds (e.g., left saccade and right key press or vice versa). While one condition only involved one set of task-relevant S-R rules, another condition involved two sets of task-relevant rules (coded by stimulus type: noise/tone), while the number of task-relevant response combinations was the same in both conditions. Here, an increase in the number of to-be-retrieved S-R rules was associated with a substantial increase in dual-response costs that were also modulated on a trial-by-trial basis when switching between rules. Taken together, the results shed further light on the dependency of cross-modal action control on both action- and rule-related memory retrieval processes.
Background/Aims:
Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement should be performed to ideally predict AKI. We investigated the association of [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass.
Methods: In a prospective cohort study, serial blood and urine samples were collected from 150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary [TIMP-2*IGFBP7] was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff was kept blinded to these results.
Results: A total of 35 patients (23.5%) experienced AKI, with a higher incidence in those with high [TIMP-2*IGFBP7] values at ICU admission (57.1% vs. 10.1%, p<0.001). In logistic regression [TIMP-2*IGFBP7] at ICU admission was independently associated with the occurrence of AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE II and CBP-time.
Conclusions: Early detection of elevated [TIMP-2*IGFBP7] at ICU admission was strongly predictive for postoperative AKI and appeared to be more precise as compared to subsequent measurements.
RNA-binding proteins (RBPs) have been established as core components of several post-transcriptional gene regulation mechanisms. Experimental techniques such as cross-linking and co-immunoprecipitation have enabled the identification of RBPs, RNA-binding domains (RBDs) and their regulatory roles in the eukaryotic species such as human and yeast in large-scale. In contrast, our knowledge of the number and potential diversity of RBPs in bacteria is poorer due to the technical challenges associated with the existing global screening approaches. We introduce APRICOT, a computational pipeline for the sequence-based identification and characterization of proteins using RBDs known from experimental studies. The pipeline identifies functional motifs in protein sequences using position-specific scoring matrices and Hidden Markov Models of the functional domains and statistically scores them based on a series of sequence-based features. Subsequently, APRICOT identifies putative RBPs and characterizes them by several biological properties. Here we demonstrate the application and adaptability of the pipeline on large-scale protein sets, including the bacterial proteome of Escherichia coli. APRICOT showed better performance on various datasets compared to other existing tools for the sequence-based prediction of RBPs by achieving an average sensitivity and specificity of 0.90 and 0.91 respectively. The command-line tool and its documentation are available at https://pypi.python.org/pypi/bio-apricot.
Somatic mutations in protein kinase A catalytic α subunit (PRKACA) were found to be causative for 30-40% of cortisol-producing adenomas (CPA) of the adrenal gland, rendering PKA signalling constitutively active. In its resting state, PKA is a stable and inactive heterotetramer, consisting of two catalytic and two regulatory subunits with the latter inhibiting PKA activity. The human genome encodes three different PKA catalytic subunits and four different regulatory subunits that are preferentially expressed in different organs. In normal adrenal glands all regulatory subunits are expressed, while CPA exhibit reduced protein levels of the regulatory subunit IIβ. In this study, we linked for the first time the loss of RIIβ protein levels to the PRKACA mutation status and found the down-regulation of RIIβ to arise post-transcriptionally. We further found the PKA subunit expression pattern of different tumours is also present in the zones of the normal adrenal cortex and demonstrate that the different PKA subunits have a differential expression pattern in each zone of the normal adrenal gland, indicating potential specific roles of these subunits in the regulation of different hormones secretion.
Predators of highly defensive prey likely develop cost-reducing adaptations. The ant Megaponera analis is a specialized termite predator, solely raiding termites of the subfamily Macrotermitinae (in this study, mostly colonies of Pseudocanthotermes sp.) at their foraging sites. The evolutionary arms race between termites and ants led to various defensive mechanisms in termites (for example, a caste specialized in fighting predators). Because M. analis incurs high injury/mortality risks when preying on termites, some risk-mitigating adaptations seem likely to have evolved. We show that a unique rescue behavior in M. analis, consisting of injured nestmates being carried back to the nest, reduces combat mortality. After a fight, injured ants are carried back by their nestmates; these ants have usually lost an extremity or have termites clinging to them and are able to recover within the nest. Injured ants that are forced experimentally to return without help, die in 32% of the cases. Behavioral experiments show that two compounds, dimethyl disulfide and dimethyl trisulfide, present in the mandibular gland reservoirs, trigger the rescue behavior. A model accounting for this rescue behavior identifies the drivers favoring its evolution and estimates that rescuing enables maintenance of a 28.7% larger colony size. Our results are the first to explore experimentally the adaptive value of this form of rescue behavior focused on injured nestmates in social insects and help us to identify evolutionary drivers responsible for this type of behavior to evolve in animals.
Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.
Division of labor is a hallmark of social insects. In the honeybee (Apis mellifera) each sterile female worker performs a series of social tasks. The most drastic changes in behavior occur when a nurse bee, who takes care of the brood and the queen in the hive, transitions to foraging behavior. Foragers provision the colony with pollen, nectar or water. Nurse bees and foragers differ in numerous behaviors, including responsiveness to gustatory stimuli. Differences in gustatory responsiveness, in turn, might be involved in regulating division of labor through differential sensory response thresholds. Biogenic amines are important modulators of behavior. Tyramine and octopamine have been shown to increase gustatory responsiveness in honeybees when injected into the thorax, thereby possibly triggering social organization. So far, most of the experiments investigating the role of amines on gustatory responsiveness have focused on the brain. The potential role of the fat body in regulating sensory responsiveness and division of labor has large been neglected. We here investigated the role of the fat body in modulating gustatory responsiveness through tyramine signaling in different social roles of honeybees. We quantified levels of tyramine, tyramine receptor gene expression and the effect of elevating fat body tyramine titers on gustatory responsiveness in both nurse bees and foragers. Our data suggest that elevating the tyramine titer in the fat body pharmacologically increases gustatory responsiveness in foragers, but not in nurse bees. This differential effect of tyramine on gustatory responsiveness correlates with a higher natural gustatory responsiveness of foragers, with a higher tyramine receptor (Amtar1) mRNA expression in fat bodies of foragers and with lower baseline tyramine titers in fat bodies of foragers compared to those of nurse bees. We suggest that differential tyramine signaling in the fat body has an important role in the plasticity of division of labor through changing gustatory responsiveness.
Differential effects of FTY720 on the B cell compartment in a mouse model of multiple sclerosis.
(2017)
Background:
MP4-induced experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), which enables targeted research on B cells, currently much discussed protagonists in MS pathogenesis. Here, we used this model to study the impact of the S1P1 receptor modulator FTY720 (fingolimod) on the autoreactive B cell and antibody response both in the periphery and the central nervous system (CNS).
Methods:
MP4-immunized mice were treated orally with FTY720 for 30 days at the peak of disease or 50 days after EAE onset. The subsequent disease course was monitored and the MP4-specific B cell/antibody response was measured by ELISPOT and ELISA. RNA sequencing was performed to determine any effects on B cell-relevant gene expression. S1P\(_{1}\) receptor expression by peripheral T and B cells, B cell subset distribution in the spleen and B cell infiltration into the CNS were studied by flow cytometry. The formation of B cell aggregates and of tertiary lymphoid organs (TLOs) was evaluated by histology and immunohistochemistry. Potential direct effects of FTY720 on B cell aggregation were studied in vitro.
Results:
FTY720 significantly attenuated clinical EAE when treatment was initiated at the peak of EAE. While there was a significant reduction in the number of T cells in the blood after FTY720 treatment, B cells were only slightly diminished. Yet, there was evidence for the modulation of B cell receptor-mediated signaling upon FTY720 treatment. In addition, we detected a significant increase in the percentage of B220\(^{+}\) B cells in the spleen both in acute and chronic EAE. Whereas acute treatment completely abrogated B cell aggregate formation in the CNS, the numbers of infiltrating B cells and plasma cells were comparable between vehicle- and FTY720-treated mice. In addition, there was no effect on already developed aggregates in chronic EAE. In vitro B cell aggregation assays suggested the absence of a direct effect of FTY720 on B cell aggregation. However, FTY720 impacted the evolution of B cell aggregates into TLOs.
Conclusions:
The data suggest differential effects of FTY720 on the B cell compartment in MP4-induced EAE.
Background:
There is a paucity of studies examining the safety of venom immunotherapy (VIT) in children. We aimed to assess the incidence of anaphylactic side effects during rush VIT in a cohort of pediatric patients and adult controls.
Methods:
72 consecutive cycles of VIT-buildup in 71 children/adolescents aged 7–17 years were retrospectively evaluated and compared to an adult control group (n = 981) with regard to baseline parameters (sex, causative venom, severity of index sting reaction, results of allergy testing, comorbidities) and the incidence of anaphylactic adverse reactions.
Results:
Compared to adults, severe index sting-induced anaphylaxis was significantly less common in children (P = .001). Children were more likely to suffer from bee venom allergy (P < .001) and showed higher levels of bee venom-specific IgE (P = .013), but lower serum tryptase concentrations (P = .014). The overall rate of VIT-induced anaphylactic reactions was higher in children than in adults (6.9% vs 2.5%, P = .046 by univariate analysis). In the final binary logistic regression model, however, only bee VIT (P = .039; odds ratio 2.25; confidence interval 1.04–4.87) and 5-day compared to 3-day buildup protocols (P = .011; odds ratio 2.64; confidence interval 1.25–5.57) were associated with an increased risk of treatment-induced anaphylaxis. All pediatric patients finally reached and tolerated the target maintenance dose of 100 µg.
Conclusions:
The higher anaphylactic reaction rate observed in pediatric patients may be attributed to a greater prevalence of bee venom allergy. VIT-induced anaphylaxis in children is usually mild and does not affect further updosing and maintenance of VIT.
Background:
In 2004, routine varicella vaccination was introduced in Germany for children aged 11–14 months. Routine measles vaccination had already been introduced in 1973 for the same age group, but coverage is still too low (<95%) in some areas to eliminate measles. The present study assessed varicella and measles vaccination coverage and determinants of parental acceptance in two study regions, situated in Northern and Southern Bavaria (Germany).
Methods:
From 2009 to 2011, annual cross-sectional parent surveys were performed on random samples of 600 children aged 18–36 months in the Bavarian regions of both Munich and Würzburg. Logistic regression models were used to identify factors associated with varicella and measles vaccination.
Results:
In 2009, 2010 and 2011, vaccination coverage was lower in Munich than in Würzburg, for both varicella (Munich 53%, 67%, 69% vs. Würzburg 72%, 81%, 83%) and for measles (Munich 88%, 89%, 91% vs. Würzburg 92%, 93%, 95%). Recommendation by the physician was the main independent factor associated with varicella vaccination in both regions (adjusted odd ratios (OR) with 95% confidence interval (CI): Munich OR 19.7, CI 13.6–28.6; Würzburg OR 34.7, CI 22.6–53.2). Attendance at a childcare unit was positively associated with a higher acceptance of varicella vaccination in Munich (OR 1.5, CI 1.1–2.2). Regarding measles vaccination, attendance at a childcare unit was positively associated in both regions (Munich OR 2.0; CI 1.3–3.0; Würzburg OR 1.8; CI 1.1–3.1), and a higher level of parental school education was negatively associated in Würzburg (OR 0.5, CI 0.3–0.9).
Conclusions:
Vaccination rates differed between regions, with rates constantly higher in Würzburg. Within each region, vaccination rates were lower for varicella than for measles. Measles vaccination status was mainly dependent upon socio-demographic factors (attendance at a childcare unit, parental school education), whereas for the more recently introduced varicella vaccination recommendation by the physician had the strongest impact. Hence, different strategies are needed to further improve vaccination rates for both diseases.
Background:
To prevent bone loss in hip arthroplasty, several short stem systems have been developed, including the Mayo conservative hip system. While there is a plethora of data confirming inherent advantages of these systems, only little is known about potential complications, especially when surgeons start to use these systems.
Methods:
In this study, we present a retrospective analysis of the patients’ outcome, complications and the complication management of the first 41 Mayo conservative hips performed in 37 patients. For this reason, functional scores, radiographic analyses, peri- and postoperative complications were assessed at an average follow-up of 35 months.
Results:
The overall HHS improved from 61.2 pre-operatively to 85.6 post-operatively. The German Extra Short Musculoskeletal Function Assessment Questionnaire (XSFMA-D) improved from 30.3 pre-operatively to 12.2 post-operatively. The most common complication was an intraoperative non-displaced fracture of the proximal femur observed in 5 cases (12.1%). Diabetes, higher BMI and older ages were shown to be risk factors for these intra-operative periprosthetic fractures (p < 0.01). Radiographic analysis revealed a good offset reconstruction in all cases.
Conclusion:
In our series, a high complication rate with 12.1% of non-displaced proximal femoral fractures was observed using the Mayo conservative hip. This may be attributed to the flat learning curve of the system or the inherent patient characteristics of the presented cohort."
Background:
Sleep-related eating may occur in the context of mental illness, sleep disorders, or psychopharmacological treatment. Frequently, sleep-related eating leads to severe weight gain and, so far, there are no treatment options for the condition.
Case presentation:
We report the case of a 54-year-old white woman with depression, panic disorder, and sleep apnea under treatment with various antidepressants who developed severe sleep-related eating. Her sleep-related eating completely vanished after addition of agomelatine, it reoccurred after cessation of agomelatine, and vanished again after her re-exposure to another melatonergic drug, extended melatonin.
Conclusions:
This case suggests that melatonergic drugs lead to relief from sleep-related eating, even when the condition occurs in the context of physical and mental disorders as well as psychopharmacological treatment.
Plants have to tightly control their energy homeostasis to ensure survival and fitness under constantly changing environmental conditions. Thus, it is stringently required that energy-consuming stress-adaptation and growth-related processes are dynamically tuned according to the prevailing energy availability. The evolutionary conserved SUCROSE NON-FERMENTING1 RELATED KINASES1 (SnRK1) and the downstream group C/S\(_{1}\) basic leucine zipper (bZIP) transcription factors (TFs) are well-characterised central players in plants’ low-energy management. Nevertheless, mechanistic insights into plant growth control under energy deprived conditions remains largely elusive. In this work, we disclose the novel function of the low-energy activated group S\(_{1}\) bZIP11-related TFs as regulators of auxin-mediated primary root growth. Whereas transgenic gain-of-function approaches of these bZIPs interfere with the activity of the root apical meristem and result in root growth repression, root growth of loss-of-function plants show a pronounced insensitivity to low-energy conditions. Based on ensuing molecular and biochemical analyses, we propose a mechanistic model, in which bZIP11-related TFs gain control over the root meristem by directly activating IAA3/SHY2 transcription. IAA3/SHY2 is a pivotal negative regulator of root growth, which has been demonstrated to efficiently repress transcription of major auxin transport facilitators of the PIN-FORMED (PIN) gene family, thereby restricting polar auxin transport to the root tip and in consequence auxin-driven primary root growth. Taken together, our results disclose the central low-energy activated SnRK1-C/S\(_{1}\)-bZIP signalling module as gateway to integrate information on the plant’s energy status into root meristem control, thereby balancing plant growth and cellular energy resources.
Background:
Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation.
Methods:
Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered.
Results:
509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9%), stage B in n = 264 (51.9%), and stage C in n = 225 (44.2%) patients; 94/225 patients were diagnosed with HFrEF (42%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19%). Overall GAI-3 of HFrEF patients was 96.4% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription.
Conclusions:
In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists.
Trial registration:
This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.
Background:
Local aortic pulse wave velocity (PWV) is a measure for vascular stiffness and has a predictive value for cardiovascular events. Ultra high field CMR scanners allow the quantification of local PWV in mice, however these systems are yet unable to monitor the distribution of local elasticities.
Methods:
In the present study we provide a new accelerated method to quantify local aortic PWV in mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at 17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) undersampling scheme, total measurement time could be reduced by a factor of 6. The fast data acquisition enables to quantify the local PWV at several locations along the aortic blood vessel based on the evaluation of local temporal changes in blood flow and vessel cross sectional area. To speed up post processing and to eliminate operator bias, we introduce a new semi-automatic segmentation algorithm to quantify cross-sectional areas of the aortic vessel. The new methods were applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE\(^{(-/-)}\)-mice) at 12 adjacent locations along the abdominal aorta.
Results:
Accelerated data acquisition and semi-automatic post-processing delivered reliable measures for the local PWV, similiar to those obtained with full data sampling and manual segmentation. No statistically significant differences of the mean values could be detected for the different measurement approaches. Mean PWV values were elevated for the ApoE\(^{(-/-)}\)-group compared to the C57BL/6J-group (3.5 ± 0.7 m/s vs. 2.2 ± 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE \(^{(-/-)}\)-animals could be observed compared to the C57BL/6J-mice, representing the local character of lesion development in atherosclerosis.
Conclusion:
In the present work, we showed that k-t BLAST PC-MRI enables the measurement of the local PWV distribution in the mouse aorta. The semi-automatic segmentation method based on PC-CMR data allowed rapid determination of local PWV. The findings of this study demonstrate the ability of the proposed methods to non-invasively quantify the spatial variations in local PWV along the aorta of ApoE\(^{(-/-)}\)-mice as a relevant model of atherosclerosis.
Background:
Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients.
Methods:
A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated.
Results:
A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7%). The rate of lymphatic fistula was 51.6 vs. 48.8%, wound infection occurred in 31.3 vs. 24.4%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected.
Conclusions:
The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional.
Background:
Although caffeine and glucocorticoids are frequently used to treat chronic lung disease in preterm neonates, potential interactions are largely unknown. While anti-inflammatory effects of glucocorticoids are well defined, their impact on airway remodeling is less characterized. Caffeine has been ascribed to positive effects on airway inflammation as well as remodeling. Connective tissue growth factor (CTGF, CCN2) plays a key role in airway remodeling and has been implicated in the pathogenesis of chronic lung diseases such as bronchopulmonary dysplasia (BPD) in preterm infants. The current study addressed the impact of glucocorticoids on the regulation of CTGF in the presence of caffeine using human lung epithelial and fibroblast cells.
Methods:
The human airway epithelial cell line H441 and the fetal lung fibroblast strain IMR-90 were exposed to different glucocorticoids (dexamethasone, budesonide, betamethasone, prednisolone, hydrocortisone) and caffeine. mRNA and protein expression of CTGF, TGF-β1-3, and TNF-α were determined by means of quantitative real-time PCR and immunoblotting. H441 cells were additionally treated with cAMP, the adenylyl cyclase activator forskolin, and the selective phosphodiesterase (PDE)-4 inhibitor cilomilast to mimic caffeine-mediated PDE inhibition.
Results:
Treatment with different glucocorticoids (1 μM) significantly increased CTGF mRNA levels in H441 (p < 0.0001) and IMR-90 cells (p < 0.01). Upon simultaneous exposure to caffeine (10 mM), both glucocorticoid-induced mRNA and protein expression were significantly reduced in IMR-90 cells (p < 0.0001). Of note, 24 h exposure to caffeine alone significantly suppressed basal expression of CTGF mRNA and protein in IMR-90 cells. Caffeine-induced reduction of CTGF mRNA expression seemed to be independent of cAMP levels, adenylyl cyclase activation, or PDE-4 inhibition. While dexamethasone or caffeine treatment did not affect TGF-β1 mRNA in H441 cells, increased expression of TGF-β2 and TGF-β3 mRNA was detected upon exposure to dexamethasone or dexamethasone and caffeine, respectively. Moreover, caffeine increased TNF-α mRNA in H441 cells (6.5 ± 2.2-fold, p < 0.05) which has been described as potent inhibitor of CTGF expression.
Conclusions:
In addition to well-known anti-inflammatory features, glucocorticoids may have adverse effects on long-term remodeling by TGF-β1-independent induction of CTGF in lung cells. Simultaneous treatment with caffeine may attenuate glucocorticoid-induced expression of CTGF, thereby promoting restoration of lung homeostasis.