Refine
Year of publication
Document Type
- Preprint (673)
- Article (439)
- Conference Proceeding (5)
- Doctoral Thesis (1)
- Part of Periodical (1)
- Working Paper (1)
Has Fulltext
- yes (1120)
Is part of the Bibliography
- no (1120)
Keywords
- Heavy Ion Experiments (20)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- LHC (9)
- Heavy-ion collision (6)
- ALICE experiment (4)
- Collective Flow (4)
- Jets (4)
- Quark-Gluon Plasma (4)
- ALICE (3)
Institute
- Physik (1056)
- Frankfurt Institute for Advanced Studies (FIAS) (958)
- Informatik (924)
- Medizin (40)
- Biowissenschaften (8)
- Geowissenschaften (4)
- Informatik und Mathematik (3)
- Biochemie und Chemie (2)
- Biodiversität und Klima Forschungszentrum (BiK-F) (2)
- Gesellschaftswissenschaften (2)
- Hochschulrechenzentrum (2)
- Sportwissenschaften (2)
- Center for Financial Studies (CFS) (1)
- ELEMENTS (1)
- Georg-Speyer-Haus (1)
- House of Finance (HoF) (1)
- Institut für Ökologie, Evolution und Diversität (1)
- Pharmazie (1)
- Psychologie (1)
- Senckenbergische Naturforschende Gesellschaft (1)
- Sustainable Architecture for Finance in Europe (SAFE) (1)
- Wirtschaftswissenschaften (1)
Objectives: Within a randomized controlled trial contrasting the outcome of manualized cognitive-behavioral (CBT) and short term psychodynamic therapy (PDT) compared to a waiting list condition (the SOPHO-Net trial), we set out to test whether self-reported attachment characteristics change during the treatments and if these changes differ between treatments.
Research design and methods: 495 patients from the SOPHO-Net trial (54.5% female, mean age 35.2 years) who were randomized to either CBT, PDT or waiting list (WL) completed the partner-related revised Experiences in Close Relationships Questionnaire (ECR-R) before and after treatment and at 6 and 12 months follow-up. The Liebowitz Social Anxiety Scale (LSAS) was administered at pre-treatment, post-treatment, and at 6-month and 1-year follow-up. ECR-R scores were first compared to a representative healthy sample (n = 2508) in order to demonstrate that the clinical sample differed significantly from the non-clinical sample with respect to attachment anxiety and avoidance.
Results: LSAS scores correlated significantly with both ECR-R subscales. Post-therapy, patients treated with CBT revealed significant changes in attachment anxiety and avoidance whereas patients treated with PDT showed no significant changes. Changes between post-treatment and the two follow-ups were significant in both conditions, with minimal (insignificant) differences between treatments at the 12- month follow-up.
Conclusions: The current study supports recent reviews of mostly naturalistic studies indicating changes in attachment as a result of psychotherapy. Although there were differences between conditions at the end of treatment, these largely disappeared during the follow-up period which is line with the other results of the SOPHO-NET trial.
Trial registration: Controlled-trials.com ISRCTN53517394
We examine the photoinduced excited state dynamics of pyrene modified adenosine, a versatile probe for folding and hybridization of ribonucleic acids. Measurements in different solvents revealed complex ultrafast dynamics, but high robustness since the overall fluorescence quantum yield (Φf) is hardly affected. The result is a strong fluorescent RNA-probe whose spectral properties change in a defined way upon environmental changes.
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive functions. Today the diagnosis of AD relies on clinical evaluations and is only late in the disease. Biomarkers for early detection of the underlying neuropathological changes are still lacking and the biochemical pathways leading to the disease are still not completely understood. The aim of this study was to identify the metabolic changes resulting from the disease phenotype by a thorough and systematic metabolite profiling approach. For this purpose CSF samples from 79 AD patients and 51 healthy controls were analyzed by gas and liquid chromatography-tandem mass spectrometry (GC-MS and LC-MS/MS) in conjunction with univariate and multivariate statistical analyses. In total 343 different analytes have been identified. Significant changes in the metabolite profile of AD patients compared to healthy controls have been identified. Increased cortisol levels seemed to be related to the progression of AD and have been detected in more severe forms of AD. Increased cysteine associated with decreased uridine was the best paired combination to identify light AD (MMSE>22) with specificity and sensitivity above 75%. In this group of patients, sensitivity and specificity above 80% were obtained for several combinations of three to five metabolites, including cortisol and various amino acids, in addition to cysteine and uridine.
Objective: The aim of the study was to analyse the psychometric properties of the EQ-5D in patients with social phobia.
Methods: We used a sample of 445 patients with social phobia with five measurement points over a 30 month period. The discriminative ability of the EQ-5D was analysed by comparing the patients' responses with the general population and between different disease severity levels. For test-retest reliability we assessed the level of agreement in patients' responses over time, when there was no change in the Liebowitz Social Anxiety Scale (LSAS). Construct validity was analysed by identifying correlations of the EQ-5D with more specific instruments. For responsiveness we compared the means of EQ VAS/EQ-5D index anchored on improved (deteriorated) health status and computed effect sizes as well as a receiver operating characteristic (ROC) curve.
Results: Compared to the general population, patients with social phobia reported more problems in the dimensions "usual activities", "pain/discomfort", and "anxiety/depression" and less problems in "mobility" and "self-care". The EQ-5D was able to distinguish between different disease severity levels. The test-retest reliability was moderate (intraclass correlation coefficient > 0.6). Correlations between the EQ-5D and other instruments were mostly small except for correlations with Beck Depression Inventory. The EQ-5D index seemed to be more responsive than the EQ VAS, but with only medium effect sizes (0.5 < effect size < 0.8) in the British EQ-5D index and only significant in patients with improved health status. The ROC analysis revealed no significant results.
Conclusions: The EQ-5D was moderately reliable and responsive in patients with improved health status. Construct validity was limited.
Trial registration: Current controlled trials ISRCTN53517394.
Background: Bidirectional promoters (BPs) are prevalent in eukaryotic genomes. However, it is poorly understood how the cell integrates different epigenomic information, such as transcription factor (TF) binding and chromatin marks, to drive gene expression at BPs. Single-cell sequencing technologies are revolutionizing the field of genome biology. Therefore, this study focuses on the integration of single-cell RNA-seq data with bulk ChIP-seq and other epigenetics data, for which single-cell technologies are not yet established, in the context of BPs.
Results: We performed integrative analyses of novel human single-cell RNA-seq (scRNA-seq) data with bulk ChIP-seq and other epigenetics data. scRNA-seq data revealed distinct transcription states of BPs that were previously not recognized. We find associations between these transcription states to distinct patterns in structural gene features, DNA accessibility, histone modification, DNA methylation and TF binding profiles.
Conclusions: Our results suggest that a complex interplay of all of these elements is required to achieve BP-specific transcriptional output in this specialized promoter configuration. Further, our study implies that novel statistical methods can be developed to deconvolute masked subpopulations of cells measured with different bulk epigenomic assays using scRNA-seq data.
Colorectal carcinoma (CRC) is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.
Background. Arterial ex situ back-table perfusion (BP) reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation.
Methods. Our prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP. The primary endpoint was the incidence of ischemic-type biliary lesions over a follow-up of 2 years after liver transplantation, whereas secondary endpoints included 2-year graft survival, initial graft damage as reflected by transaminase levels, and functional biliary parameters at 6 months after transplantation.
Results. A total of 75 livers preserved via standard aortic perfusion and 75 preserved via standard aortic perfusion plus arterial BP were treated using a standardized protocol. The incidence of clinically apparent biliary lesions after liver transplantation (n = 9 for both groups; P = 0.947), the 2-year graft survival rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP, 68%; P = 0.34), and incidence of initial graft injury did not differ between the 2 perfusion modes. Although 33 of the 77 patients with cholangiography workups exhibited injured bile ducts, only 10 had clinical symptoms.
Conclusions. Contrary to previous findings, the present study indicated that additional ex situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion injury after liver transplantation. Moreover, there was considerable discrepancy between cholangiography findings regarding bile duct changes and clinically apparent cholangiopathy after transplantation, which should be considered when assessing ischemic-type biliary lesions.
Cysteinyl leukotriene receptor 1 antagonists (CysLT1RA) are frequently used as add-on medication for the treatment of asthma. Recently, these compounds have shown protective effects in cardiovascular diseases. This prompted us to investigate their influence on soluble epoxide hydrolase (sEH) and peroxisome proliferator activated receptor (PPAR) activities, two targets known to play an important role in CVD and the metabolic syndrome. Montelukast, pranlukast and zafirlukast inhibited human sEH with IC50 values of 1.9, 14.1, and 0.8 μM, respectively. In contrast, only montelukast and zafirlukast activated PPARγ in the reporter gene assay with EC50 values of 1.17 μM (21.9% max. activation) and 2.49 μM (148% max. activation), respectively. PPARα and δ were not affected by any of the compounds. The activation of PPARγ was further investigated in 3T3-L1 adipocytes. Analysis of lipid accumulation, mRNA and protein expression of target genes as well as PPARγ phosphorylation revealed that montelukast was not able to induce adipocyte differentiation. In contrast, zafirlukast triggered moderate lipid accumulation compared to rosiglitazone and upregulated PPARγ target genes. In addition, we found that montelukast and zafirlukast display antagonistic activities concerning recruitment of the PPARγ cofactor CBP upon ligand binding suggesting that both compounds act as PPARγ modulators. In addition, zafirlukast impaired the TNFα triggered phosphorylation of PPARγ2 on serine 273. Thus, zafirlukast is a novel dual sEH/PPARγ modulator representing an excellent starting point for the further development of this compound class.
The human immunodeficiency virus (HIV) protease inhibitor saquinavir shows anticancer activity. Although its nitric oxide-modified derivative saquinavir-NO (saq-NO) was less toxic to normal cells, it exerted stronger inhibition of B16 melanoma growth in syngeneic C57BL/6 mice than saquinavir did. Saq-NO has been shown to block proliferation, upregulate p53 expression, and promote differentiation of C6 glioma and B16 cells. The anticancer activity of substances is frequently hampered by cancer cell chemoresistance mechanisms. Therefore, we here investigated the roles of p53 and the ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp), multidrug resistance-associated protein 1 (MRP1), and breast cancer resistance protein 1 (BCRP1) in cancer cell sensitivity to saq-NO to get more information about the potential of saq-NO as anticancer drug. Saq-NO exerted anticancer effects in lower concentrations than saquinavir in a panel of human cancer cell lines. Neither p53 mutation or depletion nor expression of P-gp, MRP1, or BCRP1 affected anticancer activity of saq-NO or saquinavir. Moreover, saq-NO sensitized P-gp-, MRP1-, or BCRP1-expressing cancer cells to chemotherapy. Saq-NO induced enhanced sensitization of P-gp- or MRP1-expressing cancer cells to chemotherapy compared with saquinavir, whereas both substances similarly sensitized BCRP1-expressing cells. Washout kinetics and ABC transporter ATPase activities demonstrated that saq-NO is a substrate of P-gp as well as of MRP1. These data support the further investigation of saq-NO as an anticancer drug, especially in multidrug-resistant tumors.