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

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

The vitamin D, ionised calcium and parathyroid hormone axis of cerebral capillary function: Therapeutic considerations for vascular-based neurodegenerative disorders

Blood-brain barrier dysfunction characterised by brain parenchymal extravasation of plasma proteins may contribute to risk of neurodegenerative disorders, however the mechanisms for increased capillary permeability are not understood. Increasing evidence suggests vitamin D confers central nervous system benefits and there is increasing demand for vitamin D supplementation. Vitamin D may influence the CNS via modulation of capillary function, however such effects may be indirect as it has a central role in maintaining calcium homeostasis, in concert with calcium regulatory hormones. This study utilised an integrated approach and investigated the effects of vitamin D supplementation, parathyroid tissue ablation (PTX), or exogenous infusion of parathyroid hormone (PTH) on cerebral capillary integrity. Parenchymal extravasation of immunoglobulin G (IgG) was used as a marker of cerebral capillary permeability. In C57BL/6J mice and Sprague Dawley rats, dietary vitamin D was associated with exaggerated abundance of IgG within cerebral cortex (CTX) and hippocampal formation (HPF). Vitamin D was also associated with increased plasma ionised calcium (iCa) and decreased PTH. A response to dose was suggested and parenchymal effects persisted for up to 24 weeks. Ablation of parathyroid glands increased CTX- and HPF-IgG abundance concomitant with a reduction in plasma iCa. With the provision of PTH, iCa levels increased, however the PTH treated animals did not show increased cerebral permeability. Vitamin D supplemented groups and rats with PTH-tissue ablation showed modestly increased parenchymal abundance of glial-fibrillary acidic protein (GFAP), a marker of astroglial activation. PTH infusion attenuated GFAP abundance. The findings suggest that vitamin D can compromise capillary integrity via a mechanism that is independent of calcium homeostasis. The effects of exogenous vitamin D supplementation on capillary function and in the context of prevention of vascular neurodegenerative conditions should be considered in the context of synergistic effects with calcium modulating hormones

Loss of Fibronectin in Plasma of Patients with Shock and Septicaemia and after Haemoperfusion in Patients with Severe Poisoning

Peer Reviewe

GrGen: A fast SPO-based graph rewriting tool

Graph rewriting is a powerful technique that requires graph pattern matching, which is an NP-complete problem. We present Gr-Gen, a generative programming system for graph rewriting, which applies heuristic optimizations. According to Varró’s benchmark it is at least one order of magnitude faster than any other tool known to us. Our graph rewriting tool implements the well-founded single-pushout approach. We define the notion of search plans to represent different matching strategies and equip these search plans with a cost model, taking the present host graph into account. The task of selecting a good search plan is then viewed as an optimization problem. For the ease of use, GrGen features an expressive specification language and generates program code with a convenient interface

GrapeL: Combining Graph Pattern Matching and Complex Event Processing

Incremental Graph Pattern Matching (IGPM) offers an elegant approach to find patterns in graph-based models, reporting newly added and recently removed pattern matches. However, analyzing these matches w.r.t. temporal and causal dependencies can in general only be done by extending not just the IGPM engine but also the underlying model, which often is impractical and sometimes even impossible. Therefore, we transform the stream of pattern matches to a stream of events and employ Complex Event Processing (CEP) to detect such dependencies and derive more complex events from them. For this purpose, we introduce GrapeL as a textual language to specify and generate integrated solutions using both IGPM and CEP to benefit from the synergy of both approaches, which we present in the context of a flight and booking scenario. Finally, we show that our solution can compete with an optimized hand-crafted version without GrapeL and CEP while offering a specification that yields a less tedious and error-prone design process