Neuron-to-neuron wild-type Tau protein transfer through a trans-synaptic mechanism: relevance to sporadic tauopathies.

BACKGROUND: In sporadic Tauopathies, neurofibrillary degeneration (NFD) is characterised by the intraneuronal aggregation of wild-type Tau proteins. In the human brain, the hierarchical pathways of this neurodegeneration have been well established in Alzheimer's disease (AD) and other sporadic tauopathies such as argyrophilic grain disorder and progressive supranuclear palsy but the molecular and cellular mechanisms supporting this progression are yet not known. These pathways appear to be associated with the intercellular transmission of pathology, as recently suggested in Tau transgenic mice. However, these conclusions remain ill-defined due to a lack of toxicity data and difficulties associated with the use of mutant Tau. RESULTS: Using a lentiviral-mediated rat model of hippocampal NFD, we demonstrated that wild-type human Tau protein is axonally transferred from ventral hippocampus neurons to connected secondary neurons even at distant brain areas such as olfactory and limbic systems indicating a trans-synaptic protein transfer. Using different immunological tools to follow phospho-Tau species, it was clear that Tau pathology generated using mutated Tau remains near the IS whereas it spreads much further using the wild-type one. CONCLUSION: Taken together, these results support a novel mechanism for Tau protein transfer compared to previous reports based on transgenic models with mutant cDNA. It also demonstrates that mutant Tau proteins are not suitable for the development of experimental models helpful to validate therapeutic intervention interfering with Tau spreading

Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain.

Most models for tauopathy use a mutated form of the Tau gene, MAPT, that is found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and that leads to rapid neurofibrillary degeneration (NFD). Use of a wild-type (WT) form of human Tau protein to model the aggregation and associated neurodegenerative processes of Tau in the mouse brain has thus far been unsuccessful. In the present study, we generated an original "sporadic tauopathy-like" model in the rat hippocampus, encoding six Tau isoforms as found in humans, using lentiviral vectors (LVs) for the delivery of a human WT Tau. The overexpression of human WT Tau in pyramidal neurons resulted in NFD, the morphological characteristics and kinetics of which reflected the slow and sporadic neurodegenerative processes observed in sporadic tauopathies, unlike the rapid neurodegenerative processes leading to cell death and ghost tangles triggered by the FTDP-17 mutant Tau P301L. This new model highlights differences in the molecular and cellular mechanisms underlying the pathological processes induced by WT and mutant Tau and suggests that preference should be given to animal models using WT Tau in the quest to understand sporadic tauopathies

Бокс в Томском Политехническом университете

Это первая книга о боксе в одном из томских университетов. События, факты, рассказы о боксёрах и их тренерах основаны на документальных материалах, в том числе из архивных источников, воспоминаниях ветеранов и действующих спортсменов. Это знак благодарности и признания боксёрам, тренерам и спортивным организаторам за их нелёгкую, но благодарную работу, за популяризацию бокса. В результате работы получилась содержательная и увлекательная книга, которая вызовет несомненный интерес у читателей, и будет способствовать популяризации такого замечательного вида единоборств как бокс

Two-Dimensional Electrophoresis of Tau Mutants Reveals Specific Phosphorylation Pattern Likely Linked to Early Tau Conformational Changes

The role of Tau phosphorylation in neurofibrillary degeneration linked to Alzheimer's disease remains to be established. While transgenic mice based on FTDP-17 Tau mutations recapitulate hallmarks of neurofibrillary degeneration, cell models could be helpful for exploratory studies on molecular mechanisms underlying Tau pathology. Here, “human neuronal cell lines” overexpressing Wild Type or mutated Tau were established. Two-dimensional electrophoresis highlights that mutated Tau displayed a specific phosphorylation pattern, which occurs in parallel to the formation of Tau clusters as visualized by electron microscopy. In fact, this pattern is also displayed before Tau pathology onset in a well established mouse model relevant to Tau aggregation in Alzheimer's disease. This study suggests first that pathological Tau mutations may change the distribution of phosphate groups. Secondly, it is possible that this molecular event could be one of the first Tau modifications in the neurofibrillary degenerative process, as this phenomenon appears prior to Tau pathology in an in vivo model and is linked to early steps of Tau nucleation in Tau mutants cell lines. Such cell lines consist in suitable and evolving models to investigate additional factors involved in molecular pathways leading to whole Tau aggregation

Different tau species lead to heterogeneous tau pathology propagation and misfolding.

Tauopathies are a heterogeneous group of pathologies characterized by tau aggregation inside neurons. Most of them are sporadic but certain tauopathies rely on tau gene (MAPT) mutations. They particularly differ from one to another by their different neuropathological signatures e.g. lesion shapes, regions affected and molecular composition of aggregates. Six isoforms of tau exist, but they do not all co-aggregate in each tauopathy but rather have a unique signature for each one. In some tauopathies such as Alzheimer's disease (AD), tau protein aggregation follows stereotypical anatomical stages. Recent data suggest that this progression is due to an active process of tau protein propagation from neuron-to-neuron. We wondered how tau isoforms or mutations could influence the process of tau aggregation and tau propagation. In human neuropathological material, we found that MAPT mutations induce a faster misfolding compared to tau found in sporadic AD patients. In the rat brain, we observed cell-to-cell transfer of non-pathological tau species irrespective of the tested isoform or presence of a mutation. By contrast, we found that the species of tau impact the propagation of tau pathology markers such as hyperphosphorylation and misfolding. Indeed, misfolding and hyperphosphorylated tau proteins do not spread at the same rate when tau is mutated, or the isoform composition is modified. These results clearly argue for the existence of specific folding properties of tau depending on isoforms or mutations impacting the behavior of pathological tau species

Magnetic phase formation in CoTi-substituted Ba hexaferrite coatings prepared with atmospheric plasma spraying

Thick coatings of CoTi-substituted Ba hexaferrite with the nominal composition BaCoTiFe10O19 were prepared using atmospheric plasma-spraying technology. The coatings were prepared from prereacted powders of the desired composition. The as-deposited coatings showed a high degree of crystallinity. A detailed investigation of the coatings’ phase compositions was conducted with micro-Raman spectroscopy and energy-dispersive X-ray spectroscopy. Two magnetic ferrite phases, CoTisubstituted Ba hexaferrite and Co ferrite, were identified in the coatings. An X-ray powder-diffraction analysis and a quantitative structural analysis based on Rietveld refinement showed that the mass ratio of the two phases and their chemical composition varied with respect to the spraying parameters. Consequently, the static and microwave magnetic properties of the as-sprayed coatings also varied. We were able to explain the formation of the two ferrite phases based on the interplay between the p..

Preparation of barium hexaferrite coatings using atmospheric plasma spraying

Thick coatings of barium hexaferrite with the compositions BaFe12O19 and BaCoTiFe10O19 were prepared using atmospheric plasma spraying (APS) technology. The coatings were prepared from pre-reacted powders of the desired composition. The as-deposited coatings were poorly crystallized, but their crystallinity was improved with a subsequent annealing. The crystallization mechanism of the sprayed hexaferrites was studied during annealing up to 1300 ◦C, using X-ray powder diffraction combined with thermal analysis and with electron microscopy including microanalysis. Single-phase coatings were obtained after annealing treatments at 1100–1300 ◦C. Their magnetic properties showed that they would be suitable for absorbers at microwave and mm-wave frequencies, depending on the coating phase’s composition, the crystallinity and the thicknesses

Система Эйнштейна-Эренфеста для многокомпонентного уравнения Фишера-Колмогорова-Петровского-Пискунова

For the multicomponent 1D Fisher-Kolmogorov-Petrovsky-Piskunov equation we deduce the Einstein-Ehrenfest system in the class of trajectory concentrated functions. Connection between solutions of the system and moments of the initial distributions is discussed

Thermally-sprayed BaCoTiFe10O19 layers as microwave absorbers

Microwave-absorbing layers, consisting of Co, Ti-substituted Ba-hexaferrite (BaCoTiFe10O19), were prepared by the APS and HVOF processes, using BaCoTiFe10O19 powders manufactured by solid-state reaction at 1100 \uc2\ub0C followed by spray-drying. The SEM+EDX, XRD and micro-Raman analyses indicated that the melting and quenching of the agglomerates during spraying hindered the crystallisation of the hexaferrite structure, resulting in coatings with poor magnetic properties. Adjusted processing conditions, allowing the retention of a controlled amount of unmelted material, enabled the deposition of a coating having magnetic properties close to bulk BaCoTiFe10O19, suitable for electromagnetic wave absorption. Copyright \uc2\ua9 2009 ASM International\uc2\uae All rights reserved