Actin Re-Organization Induced by Chlamydia trachomatis Serovar D - Evidence for a Critical Role of the Effector Protein CT166 Targeting Rac

The intracellular bacterium Chlamydia trachomatis causes infections of urogenital tract, eyes or lungs. Alignment reveals homology of CT166, a putative effector protein of urogenital C. trachomatis serovars, with the N-terminal glucosyltransferase domain of clostridial glucosylating toxins (CGTs). CGTs contain an essential DXD-motif and mono-glucosylate GTP-binding proteins of the Rho/Ras families, the master regulators of the actin cytoskeleton. CT166 is preformed in elementary bodies of C. trachomatis D and is detected in the host-cell shortly after infection. Infection with high MOI of C. trachomatis serovar D containing the CT166 ORF induces actin re-organization resulting in cell rounding and a decreased cell diameter. A comparable phenotype was observed in HeLa cells treated with the Rho-GTPase-glucosylating Toxin B from Clostridium difficile (TcdB) or HeLa cells ectopically expressing CT166. CT166 with a mutated DXD-motif (CT166-mut) exhibited almost unchanged actin dynamics, suggesting that CT166-induced actin re-organization depends on the glucosyltransferase motif of CT166. The cytotoxic necrotizing factor 1 (CNF1) from E. coli deamidates and thereby activates Rho-GTPases and transiently protects them against TcdB-induced glucosylation. CNF1-treated cells were found to be protected from TcdB- and CT166-induced actin re-organization. CNF1 treatment as well as ectopic expression of non-glucosylable Rac1-G12V, but not RhoA-G14A, reverted CT166-induced actin re-organization, suggesting that CT166-induced actin re-organization depends on the glucosylation of Rac1. In accordance, over-expression of CT166-mut diminished TcdB induced cell rounding, suggesting shared substrates. Cell rounding induced by high MOI infection with C. trachomatis D was reduced in cells expressing CT166-mut or Rac1-G12V, and in CNF1 treated cells. These observations indicate that the cytopathic effect of C. trachomatis D is mediated by CT166 induced Rac1 glucosylation. Finally, chlamydial uptake was impaired in CT166 over-expressing cells. Our data strongly suggest CT166's participation as an effector protein during host-cell entry, ensuring a balanced uptake into host-cells by interfering with Rac-dependent cytoskeletal changes

The value of hepatic resection in metastasic renal cancer in the era of Tyrosinkinase Inhibitor Therapy

Background: The value of liver-directed therapy (LDT) in patients with metastasic renal cell carcinoma (MRCC) is still an active field of research, particularly in the era of tyrosinkinase inhibitor (TKI) therapy. Methods: The records of 35 patients with MRCC undergoing LDT of metastasic liver lesions between 1992 and 2015 were retrospectively analyzed. Immediate postoperative TKI was given in a subgroup of patients after LDT for metastasic lesions. Uni- and multivariate models were applied to assess overall survival (OS), progression-free survival (PFS) and disease-free survival (DFS). Results: Following primary tumor (renal cell cancer) resection and LDT, respectively, median OS was better for a total of 16 patients (41 %) receiving immediate postoperative TKI with 151 and 98 months, when compared to patients without TKI therapy with 61 (p = 0.003) and 40 months (p = 0.032). Immediate postoperative TKI was associated with better median PFS (47 months versus 19 months; p = 0.023), whereas in DFS only a trend was observed (51 months versus 19 months; p = 0.110). Conclusions: LDT should be considered as a suitable additive tool in the era of TKI therapy of MRCC to the liver. In this context, postoperative TKI therapy seems to be associated with better OS and PFS, but not DFS

[Stammbuch Georg Friedrich Thalmann] / Georgius Fredericus Thalmann

[STAMMBUCH GEORG FRIEDRICH THALMANN] / GEORGIUS FREDERICUS THALMANN [Stammbuch Georg Friedrich Thalmann] / Georgius Fredericus Thalmann (1) Einband (1) Besitzvermerk (8) Einträge S. 3 - 49 (9) Einträge S. 50 - 99 (37) Einträge S. 100 - 135 (64) Register (85

[Stammbuch Georg Friedrich Thalmann] / G. F. Thalmann

[STAMMBUCH GEORG FRIEDRICH THALMANN] / G. F. THALMANN [Stammbuch Georg Friedrich Thalmann] / G. F. Thalmann (1) Einband (1) Besitzvermerk in Kartusche mit Widmung (7) Illustration: Ansicht von Jena (8) Illustration: Ansicht von Göttingen (9) Illustration: Prospect der Allee in Göttingen (10) Illustration: Äußere Hof des Universitaets Collegii in Göttingen (11) Illustration: Medicinischer Garten in Göttingen (12) Index (14) Einträge S. 10 - 49 (19) Einträge S. 50 - 99 (37) Einträge S. 100 - 150 (60) Einträge S. 151 - 200 (85) Einträge S. 201 - 250 (109) Einträge S. 251 - 302 (130) Einträge S. 303 - 336 (154

Angiotensinergic innervation of the kidney: Localization and relationship with catecholaminergic postganglionic and sensory nerve fibers

We describe an angiotensin (Ang) II-containing innervation of the kidney. Cryosections of rat, pig and human kidneys were investigated for the presence of Ang II-containing nerve fibers using a mouse monoclonal antibody against Ang II (4B3). Co-staining was performed with antibodies against synaptophysin, tyrosine 3-hydroxylase, and dopamine beta-hydroxylase to detect catecholaminergic efferent fibers and against calcitonin gene-related peptide to detect sensory fibers. Tagged secondary antibodies and confocal light or laser scanning microscopy were used for immunofluorescence detection. Ang II-containing nerve fibers were densely present in the renal pelvis, the subepithelial layer of the urothelium, the arterial nervous plexus, and the peritubular interstitium of the cortex and outer medulla. They were infrequent in central veins and the renal capsule and absent within glomeruli and the renal papilla. Ang II-positive fibers represented phenotypic subgroups of catecholaminergic postganglionic or sensory fibers with different morphology and intrarenal distribution compared to their Ang II-negative counterparts. The Ang II-positive postganglionic fibers were thicker, produced typically fusiform varicosities and preferentially innervated the outer medulla and periglomerular arterioles. Ang II-negative sensory fibers were highly varicose, prevailing in the pelvis and scarce in the renal periphery compared to the rarely varicose Ang II-positive fibers. Neurons within renal microganglia displayed angiotensinergic, cate-cholaminergic, or combined phenotypes. Our results suggest that autonomic fibers may be an independent source of intrarenal Ang II acting as a neuropeptide co-transmitter or neuromodulator. The angiotensinergic renal innervation may play a distinct role in the neuronal control of renal sodium reabsorption, vasomotion and renin secretion

Mineralization of Early Stage Carious Lesions In Vitro—A Quantitative Approach

Micro computed tomography has been combined with dedicated data analysis for the in vitro quantification of sub-surface enamel lesion mineralization. Two artificial white spot lesions, generated on a human molar crown in vitro, were examined. One lesion was treated with a self-assembling peptide intended to trigger nucleation of hydroxyapatite crystals. We non-destructively determined the local X-ray attenuation within the specimens before and after treatment. The three-dimensional data was rigidly registered. Three interpolation methods, i.e., nearest neighbor, tri-linear, and tri-cubic interpolation were evaluated. The mineralization of the affected regions was quantified via joint histogram analysis, i.e., a voxel-by-voxel comparison of the tomography data before and after mineralization. After ten days incubation, the mean mineralization coefficient reached 35.5% for the peptide-treated specimen compared to 11.5% for the control. This pilot study does not give any evidence for the efficacy of peptide treatment nor allows estimating the necessary number of specimens to achieve significance, but shows a sound methodological approach on the basis of the joint histogram analysis

Tumors in murine brains studied by grating-based phase contrast microtomography

Angiogenesis, i.e. the formation of vessels, is one of the key processes during tumor development. The newly formed vessels transport oxygen and nutrients from the healthy tissue to the tumor and gives tumor cells the possibility to replicate. The principle of anti-angiogenic therapy is to block angiogenic process in order to stop tumor growth. The aim of the present study is the investigation of murine glioma vascular architecture at early (7 days), intermediate (10 and 15 days) and late (23 days) stage of growth by means of grating-based phase contrast microtomography. We demonstrate that this technique yields premium contrast between healthy and cancerous parts of murine brain tissue

Three-dimensional and non-destructive characterization of nerves inside conduits using laboratory-based micro computed tomography

Histological assessment of peripheral nerve regeneration in animals is tedious, time-consuming and challenging for three-dimensional analysis