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Lens epithelium-derived growth factor splice variant of 75 kDa (LEDGF/p75) is an autoantigen over-expressed in solid tumors and acts as a stress-related transcriptional co-activator. Participation of autoimmune responses in the pathophysiology of benign prostatic hyperplasia (PBH) and a corresponding immunosuppressive therapy by TNFalpha antagonists has been recently suggested. Thus, autoAb testing could aid in the diagnosis of BPH patients profiting from such therapy. We generated CRISPR/Cas9 modified HEp-2 LEDGF knock-out (KO) and HEp-2 LEDGF/p75 over-expressing (OE) cells and examined IgG autoantibody reactivity to LEDGF/p75 in patients with prostate cancer (PCa, n = 89), bladder cancer (BCa, n = 116), benign prostatic hyperplasia (BPH, n = 103), and blood donors (BD, n = 60) by indirect immunofluorescence assay (IFA). Surprisingly, we could not detect elevated binding of autoAbs against LEDGF/p75 in cancer patients, but autoAb reactivity to LEDGF/p75 OE cells in about 50% of patients with BPH was unexpectedly significantly increased. Furthermore, a line immunoassay enabling the detection of 18 different autoAbs revealed a significantly increased occurrence of anti-dsDNA autoAbs in 34% of BPH patients in contrast to tumor patients and BD. This finding was confirmed by anti-mitochondrial (mDNA) autoAb detection with the Crithidia luciliae immunofluorescence test, which also showed a significantly higher prevalence (34%) of anti-mDNA autoAbs in BPH. In summary, our study provided further evidence for the occurrence of autoimmune responses in BPH. Furthermore, LEDGF/p75 over-expression renders HEp-2 cells more autoantigenic and an ideal target for autoAb analysis in BPH with a potential therapy consequence.
Background – European studies showed that women with a migration background are less likely to participate in mammography screenings than autochthonous women. However, the participation in the German mammography screening programme (MSP) among ethnic German migrants from countries of the former Soviet Union (called resettlers) is unclear so far. The aim of this study was to identify possible differences regarding MSP participation between resettlers from the FSU and the general German population.
Methods – Data from two independent, complementary studies from North Rhine-Westphalia, Germany (a retrospective cohort study 1994–2013; a cross-sectional study 2013/14) were used for comparisons between resettlers and the general population: Odds Ratios (ORs) for MSP participation utilizing the cross-sectional data and time trends of breast cancer incidence rates as well as Chi-Square tests for breast cancer stages utilizing the cohort data.
Results – Resettlers showed higher Odds to participate in the MSP than the general population (OR 2.42, 95% CI 1.08–5.42). Among resettlers, a large increase in incidence rates was observed during the MSP implementation (2005–2009), resulting in stable and comparable incidence rates after the implementation. Furthermore, pre-MSP implementation, the proportion of advanced breast cancer stages was higher among resettlers than in the German population, post-MSP implementation the proportion was comparable.
Conclusions – MSP participating seems surprisingly high among resettlers. An explanation for the increased willingness to participate might be the structured invitation procedure of the MSP. However, the exact reasons remain unclear and future research is needed to confirm this hypothesis and rule out the possibility of selection bias in the cross-sectional study.
Glyphosate (GS) inhibits the 5-enolpyruvyl-shikimate-3-phosphate (EPSP) synthase that is required for aromatic amino acid, folate and quinone biosynthesis in Bacillus subtilis and Escherichia coli. The inhibition of the EPSP synthase by GS depletes the cell of these metabolites, resulting in cell death. Here, we show that like the laboratory B. subtilis strains also environmental and undomesticated isolates adapt to GS by reducing herbicide uptake. Although B. subtilis possesses a GS-insensitive EPSP synthase, the enzyme is strongly inhibited by GS in the native environment. Moreover, the B. subtilis EPSP synthase mutant was only viable in rich medium containing menaquinone, indicating that the bacteria require a catalytically efficient EPSP synthase under nutrient-poor conditions. The dependency of B. subtilis on the EPSP synthase probably limits its evolvability. In contrast, E. coli rapidly acquires GS resistance by target modification. However, the evolution of a GS-resistant EPSP synthase under non-selective growth conditions indicates that GS resistance causes fitness costs. Therefore, in both model organisms, the proper function of the EPSP synthase is critical for the cellular viability. This study also revealed that the uptake systems for folate precursors, phenylalanine and tyrosine need to be identified and characterized in B. subtilis.