56 research outputs found

    The Carboxy-Terminal Domain of Dictyostelium C-Module-Binding Factor Is an Independent Gene Regulatory Entity

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    The C-module-binding factor (CbfA) is a multidomain protein that belongs to the family of jumonji-type (JmjC) transcription regulators. In the social amoeba Dictyostelium discoideum, CbfA regulates gene expression during the unicellular growth phase and multicellular development. CbfA and a related D. discoideum CbfA-like protein, CbfB, share a paralogous domain arrangement that includes the JmjC domain, presumably a chromatin-remodeling activity, and two zinc finger-like (ZF) motifs. On the other hand, the CbfA and CbfB proteins have completely different carboxy-terminal domains, suggesting that the plasticity of such domains may have contributed to the adaptation of the CbfA-like transcription factors to the rapid genome evolution in the dictyostelid clade. To support this hypothesis we performed DNA microarray and real-time RT-PCR measurements and found that CbfA regulates at least 160 genes during the vegetative growth of D. discoideum cells. Functional annotation of these genes revealed that CbfA predominantly controls the expression of gene products involved in housekeeping functions, such as carbohydrate, purine nucleoside/nucleotide, and amino acid metabolism. The CbfA protein displays two different mechanisms of gene regulation. The expression of one set of CbfA-dependent genes requires at least the JmjC/ZF domain of the CbfA protein and thus may depend on chromatin modulation. Regulation of the larger group of genes, however, does not depend on the entire CbfA protein and requires only the carboxy-terminal domain of CbfA (CbfA-CTD). An AT-hook motif located in CbfA-CTD, which is known to mediate DNA binding to A+T-rich sequences in vitro, contributed to CbfA-CTD-dependent gene regulatory functions in vivo

    Bioinorganic Chemistry of Alzheimer’s Disease

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    Applying Graph Transformations to Database Re-Engineering

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    modeling concepts like inheritance, aggregation, and n-ary associations cannot be expressed in the relational data model. Additionally, many physical schemas of LDAs comprise optimizations that makei teven harder to grasp the real semantics of the data structure. Hence, the first activity in the DRE process is analyze available sources of information about the LDA, in order to yield a semantically annotated database schema. The resulting annotated schema is translated into an equivalent object-oriented conceptual schema. Subsequently, the conceptual schema might be extended or used as the basis for further re-engineering activities. Both tasks, legacy schema analysis and conceptual translation, are considered to human-intensive iterative [1,5], i.e., they cannot be perfomed in a fully-automatic, batch-oriented process. The reason for this is that legacy systems vary with respect to many technical and non-technical parameters: they use various hardand software platforms and comprise arcane coding concepts [6]). Computer aided DRE tools have a great potential to reduce the complexity (2 risk) of re-engineering largeLDAs that comprise several hundred thousand 6.1

    Transcorneal electrical stimulation for the treatment of retinitis pigmentosa - a multicenter safety study of the OkuStim® System (TESOLA-study)

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    Background: Transcorneal electrical stimulation (TES) has been suggested as a possible treatment for retinitis pigmentosa (RP). Objective: To expand the safety assessment of repeated applications of an electrical current from a DTL-like electrode in patients with RP. Methods: This single-arm open label interventional safety trial included a total of 105 RP patients from 11 European centers, who received weekly TES for 6 months on 1 eye followed by observation for another 6 months without stimulation. The primary outcome measure was safety, indicated by the frequency and severity of adverse events. Secondary measures included intraocular pressure and central retinal thickness. Visual field and visual acuity were examined using the methods available at each site. Results: Dry eye sensation was the most common adverse event recorded (37.5%). Serious adverse events secondary to TES were not observed. Most adverse events were mild and all resolved without sequelae. The secondary outcome measures revealed no significant or clinically relevant changes. Conclusion: The present results confirm the excellent safety profile of TES. Transient dry eye symptoms were the most common adverse event.</p
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