RepoMed (Medizinische Hochschule Hannover)
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Synthetic Notch-Receptor-Mediated Transmission of a Transient Signal into Permanent Information via CRISPR/Cas9-Based Genome Editing.
Get PDFSynthetic receptor biology and genome editing are emerging techniques, both of which are currently beginning to be used in preclinical and clinical applications. We were interested in whether a combination of these techniques approaches would allow for the generation of a novel type of reporter cell that would recognize transient cellular events through specifically designed synthetic receptors and would permanently store information about these events via associated gene editing. Reporting cells could be used in the future to detect alterations in the cellular microenvironment, including degenerative processes or malignant transformation into cancer cells. Here, we explored synthetic Notch (synNotch) receptors expressed in human embryonic kidney cells to investigate the efficacy of antigen recognition events in a time- and dose-dependent manner. First, we evaluated the most suitable conditions for synNotch expression based on dsRed-Express fluorophore expression. Then, we used a synNotch receptor coupled to transcriptional activators to induce the expression of a Cas9 nuclease targeted to a specific genomic DNA site. Our data demonstrate that recognition of various specific antigens via synNotch receptors robustly induced Cas9 expression and resulted in an indel formation frequency of 34.5%-45.5% at the targeted CXCR4 locus. These results provide proof of concept that reporter cells can be designed to recognize a given event and to store transient information permanently in their genomes
Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells
Get PDFType 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of severe secondary complications. The incidence of T1DM has been continuously growing in the last decades, indicating an important contribution of environmental factors. Accumulating data indicates that sphingolipids may be crucially involved in T1DM development. The serum lipidome of T1DM patients is characterized by significantly altered sphingolipid composition compared to nondiabetic, healthy probands. Recently, several polymorphisms in the genes encoding the enzymatic machinery for sphingolipid production have been identified in T1DM individuals. Evidence gained from studies in rodent islets and beta-cells exposed to cytokines indicates dysregulation of the sphingolipid biosynthetic pathway and impaired function of several sphingolipids. Moreover, a number of glycosphingolipids have been suggested to act as beta-cell autoantigens. Studies in animal models of autoimmune diabetes, such as the Non Obese Diabetic (NOD) mouse and the LEW.1AR1-iddm (IDDM) rat, indicate a crucial role of sphingolipids in immune cell trafficking, islet infiltration and diabetes development. In this review, the up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given
Analyse zu Häufigkeiten, Behandlungsmethoden und Rezidivraten von Vulvadysplasien im Behandlungsgut der Frauenklinik der MHH von 2005-2010
Get PDFProf. Dr. med. Rudolf Degkwitz *19.1.1889-†21.5.1973: sein wissenschaftliches und politisches Leben vom Kaiserreich bis zur Demokratie
No full textChanging behaviour in pregnant women: a scoping review.
No full textOBJECTIVES:Behaviour change programmes (BCPs) for pregnant women are frequently implemented as part of health promotion initiatives. At present, little is known about the types of behaviour change programmes that are being implemented and whether these programmes are designed and delivered in accordance with the principles of high quality maternity care. In this scoping review, we provide an overview of existing interventions related to behaviour change in pregnancy with a particular emphasis on programmes that include empowerment components to promote autonomy and woman-led decision-making. METHODS:A systematic search strategy was applied to check for relevant papers in August 2017 and again in October 2018. RESULTS:Thirty studies met the criteria for inclusion. These studies addressed weight management, smoking cessation, general health education, nutrition, physical activity, alcohol consumption and dental health. The main approach was knowledge gain through education. More than half of the studies (n = 17) included three or more aspects of empowerment as part of the intervention. The main aspect used to foster women`s empowerment was skills and competencies. In nine studies midwives were involved, but not as programme leaders. CONCLUSIONS:Education for knowledge gain was found to be the prevailing approach in behaviour change programmes. Empowerment aspects were not a specific focus of the behaviour change programmes. This review draws attention to the need to design interventions that empower women, which may be beneficial through their live. As midwives provide maternal healthcare worldwide, they are well-suited to develop, manage, implement or assist in BCPs
The tempest in a cubic millimeter: image-based refinements necessitate the reconstruction of 3D microvasculature from a large series of damaged alternately-stained histological sections
No full textWelche Faktoren beeinflussen die Titration von Levodopa-Carbidopa Intestinal Gel-Therapie beim fortgeschrittenen idiopathischen Parkinson-Syndrom?
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