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[The microtubule-associated protein tau in neurodegenerative diseases. Tauopathies].

INTRODUCTION: Microtubules are the essential components of the cytoskeleton, they are responsible for the formation and maintenance of the neuronal morphology and their specific connections. The microtubule associated proteins (MAPs) contribute to regulate the dynamism and stability of the microtubules, and therefore they are essential to maintain the correct function of the microtubules. Among them, tau is a protein that seems to be crucial in stabilizing the neuronal polarity. DEVELOPMENT: In this paper, factors affecting the affinity of tau to bind microtubules are reviewed, giving special attention to the processes that take place in the neurodegenerative diseases that present neurofibrillary tangles (NFTs), aggregates composed of modified tau in form of paired helical filaments (PHFs). One of the most important tau modification in this aberrant aggregates is the hyperphosphorylation. Thus, kinases and phosphatases responsible for tau modification could be altered in certain pathologies, leading to a decrease in the affinity of tau to bind microtubules and carrying out its self assembling and aberrant aggregation in the neurons of the affected nervous system regions. Those pathologies presenting a tau disfunction are known as tauopathies.

Alzheimer Disease↗

Phase image analysis in Wolff-Parkinson-White syndrome. Role of transesophageal pacing.

Phase image analysis (first Fourier harmonic transformation) has been performed in 5 men with WPW syndrome to define the abnormal patterns of ventricular emptying during sinus rhythm and transesophageal pacing at different rates. All patients but one showed basal ventricular preexcitation. Of the 4 patients with basal ventricular preexcitation the earliest ventricular emptying occurred in the left ventricular free-wall in 1 patient and in the right ventricular free-wall in 3 patients. In the patient without ventricular preexcitation at rest transesophageal pacing at a rate of 100 bpm induced first ventricular activation in the left lateral ventricular free-wall while at a rate of 120 bpm it returned to normal. In the patients with ventricular preexcitation at rest, the basal image abnormalities become more evident as preexcitation was augmented. Of interest, in 1 patient with basal type B ventricular preexcitation the sequential phase image analysis, at a rate of 100 bpm confirmed the earliest ventricular activation in the right ventricular free-wall while at a rate of 120 bpm showed the earliest emptying in left ventricular free-wall suggesting the presence of 2 accessory connections. We conclude that phase mapping combined with transesophageal pacing may be a useful and reliable method to localize single as well as multiple accessory pathways in patients with ventricular preexcitation.

Adolescent↗

[Urban alternate host cycle of Taenia saginata in Wittstock County, district of Potsdam (East Germany)].

The urban alternate host cycle of Taenia saginata in the county of Wittstock, district of Potsdam (GDR). Investigations of the epidemiology of bovine cysticercosis and human taeniasis were carried out in the county of Wittstock from 1979 till 1980. The analysis was based on the examination of human faeces, sewage and sewage sludge, the registration of infested humans, anticestodica consumption, number of infested cattle, areas for squirting out sewage, fodder supply areas and location of cattle. These data were mapped. There is a direct connection between the prevalence of Cysticercus bovis in more than 50 per cent of the infested cattle of the county of Wittstock and the squirting out of the sewage of the county town. 21 to 27 million Taenia eggs per day get into the waste-water purification plant. The proportion of infested humans and infested cattle is 1: 250 or 1: 290, respectively. The prevalence of adult tapeworms is 0.008-0.18%, and that of cysticerci is 20%.

Animals↗

Human thalamus: neurochemical mapping of inferior pulvinar complex.

The primate pulvinar connects with the entire array of known visual areas and is postulated to play a role in selective visual attention. Recently, five separate neurochemical subdivisions of a region termed the inferior pulvinar (PI) complex were identified in monkeys. In the present study, similar histochemical procedures were applied to map the extent of the PI complex in humans. Acetylcholinesterase histochemistry and cytochrome oxidase staining demarcated four histochemical zones in human pulvinar, corresponding to the medial, central, lateral and lateral-shell (PI(M), PI(C), PI(L), and PI(L-S)) divisions of the PI complex in monkeys.

Acetylcholinesterase↗

Weill-Marchesani syndrome--possible linkage of the autosomal dominant form to 15q21.1.

Weill-Marchesani syndrome comprises short stature, brachydactyly, microspherophakia, glaucoma, and ectopia lentis is regarded as an autosomal recessive trait (McKusick 277600). We present two families each with affected individuals in 3 generations demonstrating autosomal dominant inheritance of Weill-Marchesani syndrome. Linkage analysis in these 2 families suggests a gene for Weill-Marchesani syndrome maps to 15q21.1. The dislocated lenses and connective tissue disorder in these families suggests that fibrillin-1 and microfibril-associated protein 1, which both map to 15q21.1, are candidate genes for Weill-Marchesani syndrome. Immunohistochemistry staining of skin sections from family 1 showed an apparent decrease in fibrillin staining compared to control individuals.

Abnormalities, Multiple↗

NotI linking clones as a tool for joining physical and genetic maps of the human genome.

To study the connection among NotI linking clones, CpG islands, and genes, the sequence surrounding 143 NotI sites was determined. These NotI linking clones were isolated from human chromosome 3-specific libraries and contain an average C + G content of 65%. These clones represent sequence-tagged sites that can be positioned onto chromosome maps and used for generating a long-range NotI map of the human genome. A majority (about 90%) of these clones contain transcribed sequences, as detected by Northern blot hybridization, providing an efficient link between physical and functional (genetic) maps. The GenBank nucleotide database was searched with sequences from these NotI linking clones. For many clones, homology was found to human and other vertebrate genes. About 20 clones contained various repeats in their sequences and may represent microsatellite loci. Most of these NotI linking clones therefore represent evolutionarily conserved DNA fragments and also can be used for comparative genome mapping of other mammalian species. In addition, approximately 20% of all sequenced human CpG island-containing genes and more than 12% of all well-characterized human genes were found to possess NotI restriction sites. This is at least 2-5 times more than has been previously estimated and suggests that NotI sites have a much stronger association with genes.

Animals↗

Mutual synchronization and clustering in randomly coupled chaotic dynamical networks.

We introduce and study systems of randomly coupled maps where the relevant parameter is the degree of connectivity in the system. Global (almost-) synchronized states are found (equivalent to the synchronization observed in globally coupled maps) until a certain critical threshold for the connectivity is reached. We further show that not only the average connectivity, but also the architecture of the couplings is responsible for the cluster structure observed. We analyze the different phases of the system and use various correlation measures in order to detect ordered nonsynchronized states. Finally, it is shown that the system displays a dynamical hierarchical clustering which allows the definition of emerging graphs.

Journal Article↗

A provisional chromosome map of Shigella and the regions related to pathogenicity.

Based on the literature and the authors' studies, the genetic markers of Shigella and the chromosome regions connected with pathogenicity are listed. A provisional map of Shigella chromosome and another provisional map indicating the chromosomal regions related to Shigella virulence have been constructed. Both maps could be useful for further genetic investigations of Shigella.

Chromosome Mapping↗

Combined Hebbian development of geniculocortical and lateral connectivity in a model of primary visual cortex.

We present a network model of visual map development in layer 4 of primary visual cortex. Our model comprises excitatory and inhibitory spiking neurons. The input to the network consists of correlated spike trains to mimick the activity of neurons in the lateral geniculate nucleus (LGN). An activity-driven Hebbian learning mechanism governs the development of both the network's lateral connectivity and feedforward projections from LGN to cortex. Plasticity of inhibitory synapses has been included into the model so as to control overall cortical activity. Even without feedforward input, Hebbian modification of the excitatory lateral connections can lead to the development of an intracortical orientation map. We have found that such an intracortical map can guide the development of feedforward connections from LGN to cortical simple cells so that the structure of the final feedforward orientation map is predetermined by the intracortical map. In a scenario in which left- and right-eye geniculocortical inputs develop sequentially one after the other, the resulting maps are therefore very similar, provided the intracortical connectivity remains unaltered. This may explain the outcome of so-called reverse lid-suture experiments, where animals are reared so that both eyes never receive input at the same time, but the orientation maps measured separately for the two eyes are nevertheless nearly identical.

Action Potentials↗

Age and sex differences in the mental realignment of maps.

Community-residing young and elderly persons were given six maps with routes indicated by lines connecting dots. The dots were arranged in a 3 x 3 matrix that corresponded to the placement of discs affixed to the testing room floor. Route lengths increased by one segment with each subsequent map. In one condition participants were instructed not to turn the map while walking the indicated route and thus the orientation of the map to the room varied as the person followed the path. In a second condition participants turned the map while following the route, keeping it aligned with the room. Elderly persons made fewer correct choices and took more time to make direction decisions than younger people as did females compared to males. When the map could not be turned, decision times were related to the amount of misalignment between the map and the room. Elderly persons, especially females were influenced more by map misalignment than were young people. The results indicate that mental realignment is an important aspect of route following and may explain some of the difficulty older people have with such tasks.

Adult↗

PRISM: topologically constrained phased refinement for macromolecular crystallography.

We describe the further development of phase refinement by iterative skeletonization (PRISM), a recently introduced phase-refinement strategy [Wilson & Agard (1993). Acta Cryst. A49, 97-104] which makes use of the information that proteins consist of connected linear chains of atoms. An initial electron-density map is generated with inaccurate phases derived from a partial structure or from isomorphous replacement. A linear connected skeleton is then constructed from the map using a modified version of Greer's algorithm [Greer (1985). Methods Enzymol. 115, 206-226] and a new map is created from the skeleton. This 'skeletonized' map is Fourier transformed to obtained new phases, which are combined with any starting-phase information and the experimental structure-factor amplitudes to produce a new map. The procedure is iterated until convergence is reached. In this paper significant improvements to the method are described as is a challenging molecular-replacement test case in which initial phases are calculated from a model containing only one third of the atoms of the intact protein. Application of the skeletonization procedure yields an easily interpretable map. In contrast, application of solvent flattening does not significantly improve the starting map. The iterative skeletonization procedure performs well in the presence of random noise and missing data, but requires Fourier data to at least 3.0 A. The constraints of linearity and connectedness prove strong enough to restore not only missing phase information, but also missing amplitudes. This enables the use of a powerful statistical test, analogous to the 'free R factor' of conventional refinement [Brünger (1992). Nature (London), 355, 472-474], for optimizing the performance of the skeletonization procedure. In the accompanying paper, we describe the application of the method to the solution of the structure of the protease inhibitor ecotin bound to trypsin and to a single isomorphous replacement problem.

Journal Article↗

A long-range restriction map of human chromosome 5q21-q23.

A long-range restriction map encompassing the APC (adenomatous polyposis coli) gene has been constructed. The map includes 35 DNA markers and consists of two segments of 10 and 2.5 Mb. Published genetic markers have been connected using additional, nonpolymorphic DNA probes. The map clarifies marker order and allows comparison of physical and genetic data.

Adenomatous Polyposis Coli↗

A genetic linkage map of rat chromosome 5 reveals extensive linkage conservation with mouse chromosome 4.

Linkages among three biochemical loci (Aco1, Ahd2, and Mup1) and four microsatellite loci (A8, Glut1, Jun, and Pnd) were determined to construct a linkage map of rat Chromosome (Chr) 5. Consequently, an extensive linkage map on rat Chr 5 was constructed with the following gene order: A8-Aco1-Mup1-Jun-Glut1-Ahd2-Pnd. In this linkage map, the Jun and A8 loci are newly placed, and two previously reported linkage groups on rat Chr 5 are connected by the Jun locus. The linkage map indicates an extensive linkage conservation between the loci on rat Chr 5 and those on mouse Chr 4.

Animals↗

Scaling self-organizing maps to model large cortical networks.

Self-organizing computational models with specific intracortical connections can explain many functional features of visual cortex, such as topographic orientation and ocular dominance maps. However, due to their computational requirements, it is difficult to use such detailed models to study large-scale phenomenal like object segmentation and binding, object recognition, tilt illusions, optic flow, and fovea-periphery differences. This article introduces two techniques that make large simulations practical. First, we show how parameter scaling equations can be derived for laterally connected self-organizing models. These equations result in quantitatively equivalent maps over a wide range of simulation sizes, making it possible to debug small simulations and then scale them up only when needed. Parameter scaling also allows detailed comparison of biological maps and parameters between individuals and species with different brain region sizes. Second, we use parameter scaling to implement a new growing map method called GLISSOM, which dramatically reduces the memory and computational requirements of large self-organizing networks. With GLISSOM, it should be possible to simulate all of human V1 at the single-column level using current desktop workstations. We are using these techniques to develop a new simulator Topographica, which will help make it practical to perform detailed studies of large-scale phenomena in topographic maps.

Animals↗

Genetic map of the beginning of the rIIB cistron of bacteriophage T4.

In this report the herefore uncharacterized mutants at the beginning of the rIIB cistron of bacteriophage T4 have been connected to the main part of the map and have been shown not to be in any way unusual. The temperature sensitive mutant HD263 appears to be the earliest mutant in the cistron.

2-Aminopurine↗

Topographic maps and molecular gradients.

Topographically organized patterns of connectivity occur throughout the central and peripheral nervous systems. It is commonly supposed that gradients of recognition molecules underlie this form of synaptic specificity. Recent studies have led to new ideas about how such gradients might arise in the retinotectal system, and initiated molecular analyses of position-dependent gene expression in the peripheral motor system.

Animals↗

Retinal repair by transplantation of photoreceptor precursors.

Photoreceptor loss causes irreversible blindness in many retinal diseases. Repair of such damage by cell transplantation is one of the most feasible types of central nervous system repair; photoreceptor degeneration initially leaves the inner retinal circuitry intact and new photoreceptors need only make single, short synaptic connections to contribute to the retinotopic map. So far, brain- and retina-derived stem cells transplanted into adult retina have shown little evidence of being able to integrate into the outer nuclear layer and differentiate into new photoreceptors. Furthermore, there has been no demonstration that transplanted cells form functional synaptic connections with other neurons in the recipient retina or restore visual function. This might be because the mature mammalian retina lacks the ability to accept and incorporate stem cells or to promote photoreceptor differentiation. We hypothesized that committed progenitor or precursor cells at later ontogenetic stages might have a higher probability of success upon transplantation. Here we show that donor cells can integrate into the adult or degenerating retina if they are taken from the developing retina at a time coincident with the peak of rod genesis. These transplanted cells integrate, differentiate into rod photoreceptors, form synaptic connections and improve visual function. Furthermore, we use genetically tagged post-mitotic rod precursors expressing the transcription factor Nrl (ref. 6) (neural retina leucine zipper) to show that successfully integrated rod photoreceptors are derived only from immature post-mitotic rod precursors and not from proliferating progenitor or stem cells. These findings define the ontogenetic stage of donor cells for successful rod photoreceptor transplantation.

Animals↗

Detection and localization of inclusions in plates using inversion of point actuated surface displacements.

A numerical simulation is carried out demonstrating the use of plate surface vibration measurements for detecting and locating inclusions within the structure. A finite element code is used to calculate normal surface displacement for both steel and mortar plates subjected to a monochromatic point force. The data is generated for the homogeneous plate and the identical plate within which exists a small rectangular inclusion. It is observed that when the elastic modulus of the inclusion is orders of magnitude lower than the base material, resonances of the inclusion produce large local displacements that are readily observed in the raw displacement data. For more modest moduli differences, there are no such directly observable effects. In this case, three inverse algorithms are used to process the displacement data. The first two are local inversion techniques that each yield a spatial map of the elastic modulus normalized by density. These algorithms successfully detect and localize the inclusion based on its modulus difference from that of the base plate. The third technique uses a form of the inhomogeneous equation of motion to obtain the induced force distribution connected with the inclusion. The spatial mapping of this force also successfully detects and localizes the inclusion.

Journal Article↗