topic study group no 12 teaching and learning of geometry primary level

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REELIN/DISABLED-1-signaling in glioma cell migration and invasion

The proteins Reelin and Disabled-1 (DAB1) are known to be key regulators in embryonal development of the central nervous system by controlling neuronal migration. Latest research revealed that Reelin/DAB1 signaling exhibits tumor suppressive functions in several cancers (e.g. hepatocellular carcinoma, breast cancer, esophageal cancer or pancreatic cancer), but until now, effects of Reelin and DAB1 on brain tumors were mostly unknown. As previous work of our laboratory indicated frequent epigenetic inactivation of Reelin in high-grade gliomas, research was pursued by examining the motility of glioblastoma cells in response to Reelin/DAB1 signaling. In the present doctoral thesis, migration and invasion of U87 and U251 cells, overexpressing either the intracellular protein DAB1 or the corresponding inactive 5F mutant, was analyzed after Reelin stimulation. Both, U87 and U251 cells, showed significantly reduced migration on fibronectin and laminin under the influence of Reelin and DAB1. Further data suggests that effects of DAB1-independent Reelin signaling, as e.g. on integrins (α3β1 and α5β1 integrin, for example), might contribute considerably to the tumor suppressive functions of this pathway. Besides this, also Reelin-independent DAB1 effects induced by other upstream mediators might play a major role in regulating glioblastoma invasion. Further experiments comprised matrigel invasion assays as well as the investigation of the underlying downstream targets of Reelin and DAB1. Taken together, Reelin and DAB1 were identified as novel players in the regulation of glioblastoma cell migration suggesting tumor suppressive functions of Reelin/DAB1 signaling in high-grade gliomas

Cementless femoral components in bicondylar hybrid knee arthroplasty in patients with rheumatoid arthritis: A 10-year survivorship analysis

Background: Total knee arthroplasty (TKA) has been established as a successful surgical treatment in the late stages of rheumatoid joint destruction. The purpose of this study was to review the clinical outcome and survivorship in rheumatoid arthritis (RA) patients undergoing TKA in hybrid technique with a cementless fixation of the femoral component. Methods: We analysed retrospectively 66 RA patients who underwent 72 TKAs (P.F.C. Sigma®). Mean follow-up time was 124 ± 41 months. To evaluate postoperative clinical outcome, knee injury and osteoarthritis outcome score (KOOS) and Oxford knee score (OKS) were assessed. Kaplan–Meier analysis was used to calculate survivorship. The primary outcome was revision for any reason. Results: Thirty-four patients (36 knees) died and two patients (2 knees) were lost to follow-up. Three patients (four knees) did not agree to participate. Twenty-seven patients (30 knees) were available for assessing clinical scores. The average scores were 85 ± 14 for KOOS and 34 ± 10 for OKS. In three patients (three knees), revision was necessary, including restricted range of motion (n = 1), instability (n = 1), and infection (n = 1). There were no cases of loosening in this cohort study. The survival rates were 100% at 5 years, 97.1% at 10 years (95% CI 89.0–99.2%) and 95.6% at 15 years (95% CI 86.9–98.5%). Conclusions: This study confirms that excellent clinical results and a good 10-year survivorship can be obtained with hybrid fixation technique in TKA in the unique population of RA patients

Macrophage Migration Inhibitory Factor in Major Depressive Disorder: A Multilevel Pilot Study

Macrophage migration inhibitory factor (MIF) is a controversially discussed inflammatory marker in major depressive disorder (MDD). While some studies show an association of high MIF protein levels with depression, animal models have yielded conflicting results. Thus, it remains elusive as to whether MIF plays an anti- or pro-depressive role. Therefore, we aimed to examine the potential of MIF at the genetic, expression and protein levels as a risk factor and biomarker to diagnose, monitor, or predict the course of MDD. Patients with a current major depressive episode (n = 66 with, and n = 63 without, prior medication) and remitted patients (n = 39) were compared with healthy controls (n = 61). Currently depressed patients provided a second blood sample after three weeks of therapy. Depression severity was assessed by self-evaluation and clinician rating scales. We genotyped for three MIF polymorphisms and analyzed peripheral MIF expression and serum levels. The absence of minor allele homozygous individuals in the large group of 96 female patients compared with 10–16% in female controls suggests a protective effect for MDD, which was not observed in the male group. There were no significant group differences of protein and expression levels, however, both showed predictive potential for the course of depression severity in some subgroups. While MIF protein levels, but not MIF expression, decreased during treatment, they were not associated with changes in depression severity. This project is the first to investigate three biological levels of MIF in depression. The data hint toward a genetic effect in women, but do not provide robust evidence for the utility of MIF as a biomarker for the diagnosis or monitoring of MDD. The observed predictive potential requires further analysis, emphasizing future attention to confounding factors such as sex and premedication

Trefoil Factor 3 (TFF3) Is Involved in Cell Migration for Skeletal Repair

The aim of the study was to explore the possible role of Trefoil Factor Family peptide 3 (TFF3) for skeletal repair. The expression of TFF3 was analyzed in human joint tissues as well as in a murine bone fracture model. Serum levels of TFF3 following a defined skeletal trauma in humans were determined by ELISA. The mRNA expression of TFF3 was analyzed under normoxia and hypoxia. Expression analysis after stimulation of human mesenchymal progenitor cells (MPCs) with TFF3 was performed by RT2 Profiler PCR Array. The effect of recombinant human (rh)TFF3 on MPCs was analysed by different migration and chemotaxis assays. The effect on cell motility was also visualized by fluorescence staining of F-Actin. TFF3 was absent in human articular cartilage, but strongly expressed in the subchondral bone and periosteum of adult joints. Strong TFF3 immunoreactivity was also detected in murine fracture callus. Serum levels of TFF3 were significantly increased after skeletal trauma in humans. Expression analysis demonstrated that rhTFF3 significantly decreased mRNA of ROCK1. Wound healing assays showed increased cell migration of MPCs by rhTFF3. The F-Actin cytoskeleton was markedly influenced by rhTFF3. Cell proliferation was not increased by rhTFF3. The data demonstrate elevated expression of TFF3 after skeletal trauma. The stimulatory effects on cell motility and migration of MPCs suggest a role of TFF3 in skeletal repair