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

Neural correlates of sound localization in a multisound environment

Localizing and identifying sounds when multiple sound sources are competing is an every day experience. This was described by Cherry (1953) as the cocktail party phenomenon. Although this effect has been extensively studied, it is still insufficiently understood how the brain is able to filter the stimulus of interest from the overall auditory information received. Our purpose was to investigate the underlying neural correlates of the cocktail party effect by functional magnetic resonance imaging, implementing a sound localization task with multiple competing sounds. Our results indicate that mainly identical areas are involved in active localization of sound sources presented in complex environments and in isolation. The auditory spatial attention network, overlaps the localization network primarily in IPL, MFG, and IFG. These latter areas correspond to the area of overlap of both dorsal and ventral attention networks described for visual processing, thus suggesting attentional processing of multisensory spatial information in these areas

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