A multilevel account of hippocampal function in spatial and concept learning: Bridging models of behavior and neural assemblies

A complete neuroscience requires multilevel theories that address phenomena ranging from higher-level cognitive behaviors to activities within a cell. We propose an extension to the level of mechanism approach where a computational model of cognition sits in between behavior and brain: It explains the higher-level behavior and can be decomposed into lower-level component mechanisms to provide a richer understanding of the system than any level alone. Toward this end, we decomposed a cognitive model into neuron-like units using a neural flocking approach that parallels recurrent hippocampal activity. Neural flocking coordinates units that collectively form higher-level mental constructs. The decomposed model suggested how brain-scale neural populations coordinate to form assemblies encoding concept and spatial representations and why so many neurons are needed for robust performance at the cognitive level. This multilevel explanation provides a way to understand how cognition and symbol-like representations are supported by coordinated neural populations (assemblies) formed through learning

Preliminary Observations on the Effects In Vivo and In Vitro of Low Dose Laser on the Epithelia of the Bladder, Trachea and Tongue of the Mouse

The effects of low dose CW laser were studied by in vivo and in vitro systems. The experimental tissues that were used included bladders, tracheas and tongues as experimental tissues. Buddings (round surface projections) from the transitional epithelium of bladder were frequently observed 3 days after laser treatment in both in vivo and in vitro systems. The trachea and tongue were less affected. In both the in vivo and in vitro systems, some epithelial cells of the trachea showed decreased microvilli and cilia 3 days after treatment whereas the epithelial cells of the tongue revealed no response to laser treatment in both systems. Low dose laser, however, appeared to promote the rate of healing of experimental tongue ulcer: healing was about 1 day earlier in the laser treated than non-treated animals and vessel infiltration and epithelialization were detected earlier in the treated

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

The molecular events that drive the initiation and progression of ovarian adenocarcinoma are not well defined. We have investigated changes in gene expression in ovarian cancer cell lines compared to an immortalized human ovarian surface epithelial cell line (HOSE) using a cDNA array. We identified 17 genes that were under-expressed and 10 genes that were over-expressed in the cell lines compared to the HOSE cells. One of the genes under-expressed in the ovarian cancer cell lines, Id3, a transcriptional inactivator, was selected for further investigation. Id3 mRNA was expressed at reduced levels in 6 out of 9 ovarian cancer cell lines compared to the HOSE cells while at the protein level, all 7 ovarian cancer cell lines examined expressed the Id3 protein at greatly reduced levels. Expression of Id3 mRNA was also examined in primary ovarian tumours and was found in only 12/38 (32%) cases. A search was conducted for mutations of Id3 in primary ovarian cancers using single stranded conformation polymorphism (SSCP) analysis. Only one nucleotide substitution, present also in the corresponding constitutional DNA, was found in 94 ovarian tumours. Furthermore no association was found between LOH at 1p36 and lack of expression of Id3. These data suggest that Id3 is not the target of LOH at 1p36. © 2001 Cancer Research Campaign http://www.bjcancer.co

Lymphocyte apoptosis, macrophage function and disease activity in systemic lupus erythematosus

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Development of Shear Modulus Reduction Curves Based on Lotung Downhole Ground Motion Data

In this study, equivalent shear moduli (or shear-wave velocities) and their variations with shearing strain at the Lotung seismic experiment site were back-calculated from recorded downhole array ground motions. Ground motion data for various levels of shaking (peak ground surface accelerations ranging from 0.03g to 0.21g) recorded during seven earthquakes were used in the analyses. Results show that downhole array ground motion data can be used to infer in-situ dynamic soil properties over a wide strain range

Occurrence and experimental infection of toads (Bufo marinus and B. granulosus) with mycobacterium chelonei subsp. abscessus

In a survey of 234 Amazonian toads and frogs, six strains of Mycobacterium chelonei subsp. abscessus were isolated from the liver or spleen of four of 66 Bufo marinus (6.1%) and from the kidney or peritoneal fluid of two of 86 B. granulosus (2.3%). There were no histopathological lesions in the viscera of the infected animals. Experimental infection of 29 captive B. marinus and B. granulosus, by the intraperitoneal route, with a pooled inoculum of M. chelonei subsp. abscessus caused five deaths near the end of a 2-month observation period. M. chelonei subsp. abscessus was isolated from the liver, spleen, kidney, gonad, heart and lung of toads killed at various intervals after inoculation, and intracellular acid-fast bacilli were seen in these organs. Histological evidence of invasion of tissues by mycobacteria became apparent from the 45th day after infection. The susceptibility to infection of B. marinus and B. granulosus suggests that these toads may serve as a fortuitous animal host for M. chelonei subsp. abscessus

Stimulation of Collagen Formation in the Intestinal Anastomosis by Low Dose He-Ne Laser

The effect of low dose He-Ne laser on the healing of intestinal anastomosis was studied in the albino rat. A small piece of jejunum was removed from each rat and the ends sutured back with a simple interrupted pattern. In the experimental animal, the anastomosis was Irradiated through an optic fiber with a He-Ne laser (1 mW) for 15 minutes whereas in the control animal, the anastomosis was not irradiated. The differences between the two groups were compared by histology, transmission electron microscopy, scanning electron microscopy and autoradiography 3 and 7 days after operation. The laser treated experimental animals demonstrated thicker collagen fibers and an increased quantity of collagen at the junction of the anastomosis compared to control animals. Increased uptake of labelled proline was also evident in the laser treated animals. These observations all point to a possible enhancement of collagen synthesis triggered by laser irradiation

Dynamic Soil-Foundation-Structure Interaction Analyses of Large Caissons

Large cellular reinforced concrete caissons exist as foundations of major long-span bridges across waterways in many parts of the country. This study was conducted to evaluate the important factors affecting the seismic response of large caissons. The paper presents the results of equivalent linear and non-linear analyses performed for a typical caisson idealized based on the cellular caisson at Pier W3 of the West San Francisco Bay Bridge subject to ground motion with a peak rock acceleration of 0.6 g. This caisson is 38.7 m (127 fi) long by 22.9 m (75 ft) wide submerged in about 32.6 m (107 ft) of water. It is embedded in 33.5 m (110 fi) of soil deposits and is founded on rock. Equivalent linear 3-D and 2-D analyses conducted in the direction of the short axis (longitudinal) were performed using a modified version of computer program SASSI. The results of these 3-D and 2-D analyses are similar. Non-linear analyses were performed for 2-D models using computer program FLAC. The results indicate that side gapping, base lifting, interface sliding, and soil yielding reduce the earth pressure, base bearing stress, caisson shear and bending moment, and caisson motions. However, the frequency characteristics of the responses appear to be relatively unaffected

The thorny issue of choosing outcome measures for aphasia therapy trials: A comparison of discourse and aphasia battery outcomes following Multi-modality and Constraint Induced aphasia therapy

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Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

BackgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.MethodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.ResultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.ConclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy