Charité

About: Charité is a healthcare organization based out in Berlin, Germany. It is known for research contribution in the topics: Population & Transplantation. The organization has 30624 authors who have published 64507 publications receiving 2437322 citations. The organization is also known as: Charite & Charité – University Medicine Berlin.

Correlation between circulating CD27high plasma cells and disease activity in patients with systemic lupus erythematosus.

Abstract: Objective Disease activity in systemic lupus erythematosus (SLE) is usually assessed with complex disease activity scores comprising a variety of different parameters In order to determine whether SLE disease activity correlates with abnormal B lymphocyte activity, B cell subsets were analyzed, and their relationship to clinical and humoral measures of disease activity was assessed Methods The distribution of B cell subsets was determined by fluorescence-activated cell sorting analysis and assessed in relation to the autoantibody profile, disease activity measured by the SLE Disease Activity Index (SLEDAI) and the European Consensus Lupus Activity Measure scores, disease duration, and therapy Results The number and frequency of CD27high plasma cells were significantly correlated with the SLE disease activity indices and with the titer of anti–double-stranded DNA (anti-dsDNA) autoantibodies Circulating B cell subsets were not influenced by age or sex, but appeared to relate to the duration of disease and the therapeutic regimen, with the number and frequency of CD27high plasma cells increasing and those of CD27− naive B cells decreasing over time Patients were divided into those with a SLEDAI score of 0–8 (low disease activity) and those with SLEDAI score >8 (high disease activity) Patients with high disease activity had an increased frequency of both CD19+ B cells and CD27high plasma cells By using a nonparametric data sieving algorithm, we observed that these B cell abnormalities provided predictive values for nonactive and active disease of 780% and 789%, respectively The predictive value of the B cell abnormalities (789%) was greater than that of the humoral/clinical data pattern (714%), including anti-dsDNA antibody levels, circulating immune complexes, increased erythrocyte sedimentation rate, mucocutaneous involvement, and acute renal involvement Conclusion Flow cytometric monitoring of B cell subsets in the peripheral blood provides new insights into abnormalities of B cell function in SLE and may also be a diagnostically valuable option for monitoring the activity of this autoimmune disease

Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS)

Abstract: PERIOD (PER) proteins are central components within the mammalian circadian oscillator, and are believed to form a negative feedback complex that inhibits their own transcription at a particular circadian phase. Phosphorylation of PER proteins regulates their stability as well as their subcellular localization. In a systematic screen, we have identified 21 phosphorylated residues of mPER2 including Ser 659, which is mutated in patients suffering from familial advanced sleep phase syndrome (FASPS). When expressing FASPS-mutated mPER2 in oscillating fibroblasts, we can phenocopy the short period and advanced phase of FASPS patients’ behavior. We show that phosphorylation at Ser 659 results in nuclear retention and stabilization of mPER2, whereas phosphorylation at other sites leads to mPER2 degradation. To conceptualize our findings, we use mathematical modeling and predict that differential PER phosphorylation events can result in opposite period phenotypes. Indeed, interference with specific aspects of mPER2 phosphorylation leads to either short or long periods in oscillating fibroblasts. This concept explains not only the FASPS phenotype, but also the effect of the tau mutation in hamster as well as the doubletime mutants (dbt S and dbt L )i nDrosophila.

Mass spectrometry-based metabolic profiling reveals different metabolite patterns in invasive ovarian carcinomas and ovarian borderline tumors.

Abstract: Metabolites are the end products of cellular regulatory processes, and their levels can be regarded as the ultimate response of biological systems to genetic or environmental changes. We have used a metabolite profiling approach to test the hypothesis that quantitative signatures of primary metabolites can be used to characterize molecular changes in ovarian tumor tissues. Sixty-six invasive ovarian carcinomas and nine borderline tumors of the ovary were analyzed by gas chromatography/time-of-flight mass spectrometry (GC-TOF MS) using a novel contamination-free injector system. After automated mass spectral deconvolution, 291 metabolites were detected, of which 114 (39.1%) were annotated as known compounds. By t test statistics with P < 0.01, 51 metabolites were significantly different between borderline tumors and carcinomas, with a false discovery rate of 7.8%, estimated with repeated permutation analysis. Principal component analysis (PCA) revealed four principal components that were significantly different between both groups, with the highest significance found for the second component (P = 0.00000009). PCA as well as additional supervised predictive models allowed a separation of 88% of the borderline tumors from the carcinomas. Our study shows for the first time that large-scale metabolic profiling using GC-TOF MS is suitable for analysis of fresh frozen human tumor samples, and that there is a consistent and significant change in primary metabolism of ovarian tumors, which can be detected using multivariate statistical approaches. We conclude that metabolomics is a promising high-throughput, automated approach in addition to functional genomics and proteomics for analyses of molecular changes in malignant tumors.