Molecular dissection of ephrinB reverse signaling

Synapses form when highly motile dendritic filopodia establish axonal contacts. When a synaptic contact is stabilized, it gives rise to the formation of a dendritic spine, which has recently been shown to involve a number of molecules that mostly regulate the actin cytoskeleton. Thus, it is not surprising that Eph receptor tyrosine kinases, as known regulators of signaling pathways involved in actin cytoskeleton remodeling, have been shown to be required for spine development and maintenance. The main characteristic of interactions of the Eph receptor with its membrane associated ephrin ligand is that they can propagate bidirectional signals. Both forward (downstream of Eph receptor) and reverse (downstream of ephrin ligand) signaling have been shown to play a role in mature synapses, where spine morphology changes are associated with synaptic plasticity. Thus, ephrinB reverse signaling might be as important for dendritic spine development as signaling pathways downstream of Eph receptors. Intrigued by this idea, we hypothesized that some of the spine morphology changes during plasticity might be regulated exclusively by ephrin reverse signaling pathways. Analyzing spine formation in cultures of dissociated hippocampal neurons, we demonstrated that stimulation of hippocampal neurons with EphB receptor bodies leads to increased spine maturation. Expression of a truncated form of ephrinB ligand, which is still able to activate EphB receptor but is unable to transduce intracellular signals, impairs spine morphology. To find new players of reverse signaling that are important in directing ephrin-mediated spine morphology, we performed a proteomic analysis of the phosphotyrosine dependent ephrin interactor Grb4 (Nck-2, Nck beta). We identified the signaling adaptor G protein-coupled receptor kinase-interacting protein (GIT)1 (Cat1) as well as the exchange factor for Rac βPIX (β-p21-activated protein kinase (PAK)-interacting exchange factor), also called RhoGEF7 or Cool-1, as novel Grb4 binding partners, which have both previously been shown to be required for spine formation. We show that Grb4 binds and recruits GIT1 to synapses downstream of activated ephrinB ligand. Interactions of Grb4 with ephrin or GIT1 are necessary for proper spine morphogenesis and synapse formation. We therefore provide evidence for an important role of ephrinB reverse signaling in spine formation and describe the ephrinB reverse signaling pathway involved in this process

Can we prevent or treat multiple sclerosis by individualised vitamin D supply?

Apart from its principal role in bone metabolism and calcium homeostasis, vitamin D has been attributed additional effects including an immunomodulatory, anti-inflammatory, and possibly even neuroprotective capacity which implicates a possible role of vitamin D in autoimmune diseases like multiple sclerosis (MS). Indeed, several lines of evidence including epidemiologic, preclinical, and clinical data suggest that reduced vitamin D levels and/or dysregulation of vitamin D homeostasis is a risk factor for the development of multiple sclerosis on the one hand, and that vitamin D serum levels are inversely associated with disease activity and progression on the other hand. However, these data are not undisputable, and many questions regarding the preventive and therapeutic capacity of vitamin D in multiple sclerosis remain to be answered. In particular, available clinical data derived from interventional trials using vitamin D supplementation as a therapeutic approach in MS are inconclusive and partly contradictory. In this review, we summarise and critically evaluate the existing data on the possible link between vitamin D and multiple sclerosis in light of the crucial question whether optimization of vitamin D status may impact the risk and/or the course of multiple sclerosis

Chemistry of Secondary Polyphenols Produced during Processing of Tea and Selected Foods

This review will discuss recent progress in the chemistry of secondary polyphenols produced during food processing. The production mechanism of the secondary polyphenols in black tea, whisky, cinnamon, and persimmon fruits will be introduced. In the process of black tea production, tea leaf catechins are enzymatically oxidized to yield a complex mixture of oxidation products, including theaflavins and thearubigins. Despite the importance of the beverage, most of the chemical constituents have not yet been confirmed due to the complexity of the mixture. However, the reaction mechanisms at the initial stages of catechin oxidation are explained by simple quinone–phenol coupling reactions. In vitro model experiments indicated the presence of interesting regio- and stereoselective reactions. Recent results on the reaction mechanisms will be introduced. During the aging of whisky in oak wood barrels, ellagitannins originating from oak wood are oxidized and react with ethanol to give characteristic secondary ellagitannins. The major part of the cinnamon procyanidins is polymerized by copolymerization with cinnamaldehyde. In addition, anthocyanidin structural units are generated in the polymer molecules by oxidation which accounts for the reddish coloration of the cinnamon extract. This reaction is related to the insolubilization of proanthocyanidins in persimmon fruits by condensation with acetaldehyde. In addition to oxidation, the reaction of polyphenols with aldehydes may be important in food processing

Metabolic Changes in the Visual Cortex Are Linked to Retinal Nerve Fiber Layer Thinning in Multiple Sclerosis

OBJECTIVE: To investigate the damage to the retinal nerve fiber layer as part of the anterior visual pathway as well as an impairment of the neuronal and axonal integrity in the visual cortex as part of the posterior visual pathway with complementary neuroimaging techniques, and to correlate our results to patients' clinical symptoms concerning the visual pathway. DESIGN, SUBJECTS AND METHODS: Survey of 86 patients with relapsing-remitting multiple sclerosis that were subjected to retinal nerve fiber layer thickness (RNFLT) measurement by optical coherence tomography, to a routine MRI scan including the calculation of the brain parenchymal fraction (BPF), and to magnetic resonance spectroscopy at 3 tesla, quantifying N-acetyl aspartate (NAA) concentrations in the visual cortex and normal-appearing white matter. RESULTS: RNFLT correlated significantly with BPF and visual cortex NAA, but not with normal-appearing white matter NAA. This was connected with the patients' history of a previous optic neuritis. In a combined model, both BPF and visual cortex NAA were independently associated with RNFLT. CONCLUSIONS: Our data suggest the existence of functional pathway-specific damage patterns exceeding global neurodegeneration. They suggest a strong interrelationship between damage to the anterior and the posterior visual pathway

Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts seem to be such a promising and safe alternative. However, data regarding the beneficial effects and possible underlying mechanism, specifically in clinical trials, are rare and rather controversial or non-conclusive. This review outlines the existing evidence from preclinical studies (cell and tissue cultures and animal models) and clinical trials regarding preventive and therapeutic effects of epigallcatechin-3-gallate in neurodegenerative diseases and considers antioxidative vs. pro-oxidative properties of the tea catechin important for dosage recommendations

Application of e-learning technologies in the educational process as pedagogical problem

The paper presents the pedagogical problem of the e-learning technologies integration in the system of Russian higher education. The integration of e-learning technologies into the educational process of Russian universities and institutes meets many difficulties, such as technical and psychological ones. In this case, the theory of staff motivation can become an actual solution. The theoretical part of the research deals with the phenomenon of motivation, its types and theories. Also, the phenomenon of e-learning is analyzed as well as its advantages and disadvantages. The applied part of the paper is devoted to the development of motivation criteria for integrating e-learning technologies into the educational process of Russian universities