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Biomedical subjects

X B Wu

Publications and source records attributed to X B Wu.

11 recordsLinked to original sources
PubMed2002

Initial state randomness improves sequence learning in a model hippocampal network.

Randomness can be a useful component of computation. Using a computationally minimal, but still biologically based model of the hippocampus, we evaluate the effects of initial state randomization on learning a cognitive problem that requires this brain structure. Greater randomness of initial states leads to more robust performance in simulations of the cognitive task called transverse patterning, a context-dependent discrimination task that we code as a sequence prediction problem. At the conclusion of training, greater initial randomness during training trials also correlates with increased, repetitive firing of select individual neurons, previously named local context neurons. In essence, such repetitively firing neurons recognize subsequences, and previously their presence has been correlated with solving the transverse patterning problem. A more detailed analysis of the simulations across training trials reveals more about initial state randomization. The beneficial effects of initial state randomization derive from enhanced variation, across training trials, of the sequential states of a network. This greater variation is not uniformly present during training; it is largely restricted to the beginning of training and when novel sequences are introduced. Little such variation occurs after extensive or even moderate amounts of training. We explain why variation is high early in training, but not later. This automatic modulation of the initial-state-driven random variation through state space is reminiscent of simulated annealing where modulated randomization encourages a selectively broad search through state space. In contrast to an annealing schedule, the selective occurrence of such a random search here is an emergent property, and the critical randomization occurs during training rather than testing.

Animals↗
PubMed2002

Differential effects of interleukin-6 receptor activation on intracellular signaling and bone resorption by isolated rat osteoclasts.

The effects of the related cytokines interleukin-6 (IL-6), leukemia inhibitory factor (LIF) and oncostatin-M on bone resorption and cytosolic Ca(2+) signaling were compared in isolated rat osteoclasts. In the traditional disaggregated osteoclast (pit) assay, IL-6 and LIF, but not oncostatin-M, conserved the bone resorption otherwise inhibited by high extracellular [Ca(2+)] (15 mM). It produced a paradoxical, concentration-dependent stimulation of resorption by elevated extracellular Ca(2+). In the micro-isolated single osteoclast resorption assay, IL-6, high [Ca(2+)] or IL-6 plus high [Ca(2+)] all increased pit formation. In contrast, the IL-6 receptor (IL-6R)-specific agonist antibody MT-18 inhibited bone resorption in a concentration-dependent manner (1:500 to 1:500 000). MT-18 triggered cytosolic Ca(2+) signals in fura 2-loaded osteoclasts within approximately 10 min of application. Each cytosolic Ca(2+) transient began with a peak deflection that persisted in Ca(2+)-free, EGTA-containing extracellular medium, consistent with a release of intracellularly stored Ca(2+). This was followed by a sustained elevation of cytosolic [Ca(2+)] that was abolished in Ca(2+)-free medium, as expected from an entry of extracellular Ca(2+), and by the Ca(2+) channel antagonist Ni(2+). The inclusion of either IL-6 or soluble human (sh) IL-6R specifically reversed both the above effects of MT-18, confirming that both effects were specific for the IL-6R. The findings suggest that IL-6R activation by IL-6 stimulates osteoclastic bone resorption either by reversing the inhibitory effect of high extracellular Ca(2+) in stromal-containing systems or itself stimulating bone resorption along with Ca(2+) by micro-isolated osteoclasts. In contrast, activation of the IL-6R by an agonist antibody produces an inhibition of bone resorption and an associated triggering of the cytosolic Ca(2+) signals previously associated with regulation of bone resorptive function in other situations.

Animals↗
PubMed2000

Molecular cloning, expression, and functional characterization of a novel member of the CD38 family of ADP-ribosyl cyclases.

We report the molecular cloning and functional characterization of a novel member of the CD38 family of cyclic ADP-ribose (cADPr)-generating cyclases. We cloned a cDNA insert that encoded a 298-amino-acid-long protein (M(w) approximately 39 kDa). The predicted protein displayed 69, 61, and 58% similarity, respectively, to mouse, rat, and human CD38. Rabbit CD38 was also 28% homologous to Aplysia ADP-ribosyl cyclase and leukocyte CD157 (another ADP-ribosyl cyclase); the three cyclases shared 10 cysteine and 2 adjacent proline residues. We then transfected CD38-negative NIH3T3 cells with cDNA encoding a CD38-EGFP fusion protein. Epifluorescence microscopy showed intense EGFP fluorescence confirming CD38 expression. We finally confirmed the ADP-ribosyl cyclase activity of the expressed CD38 by measuring its ability to catalyze the cyclization of the nicotinamide adenine dinucleotide (NAD(+)) surrogate, NGD(+), to its fluorescent nonhydrolyzable derivative, cGDPr.

3T3 Cells↗
PubMed2000

Controlling activity fluctuations in large, sparsely connected random networks.

Controlling activity in recurrent neural network models of brain regions is essential both to enable effective learning and to reproduce the low activities that exist in some cortical regions such as hippocampal region CA3. Previous studies of sparse, random, recurrent networks constructed with McCulloch-Pitts neurons used probabilistic arguments to set the parameters that control activity. Here, we extend this work by adding an additional, biologically appropriate, parameter to control the magnitude and stability of activity oscillations. The new constant can be considered to be the rest conductance in a shunting model or the threshold when subtractive inhibition is used. This new parameter is critical for large networks run at low activity levels. Importantly, extreme activity fluctuations that act to turn large networks totally on or totally off can now be avoided. We also show how the size of external input activity interacts with this parameter to affect network activity. Then the model based on fixed weights is extended to estimate activities in networks with distributed weights. Because the theory provides accurate control of activity fluctuations, the approach can be used to design a predictable amount of pseudorandomness into deterministic networks. Such nonminimal fluctuations improve learning in simulations trained on the transitive inference problem.

Computer Simulation↗
PubMed1998

[Adeno-associated virus vector mediated gene transfer of HSVI-TK and its effect on killing cancer cell].

The plasmid pACTK-19 was constructed by inserting HSVI-TK gene into the multiple cloning sites of the general adeno-associated virus(AAV) vector pACR-Neo. When plasmid pACTK-19 was transfected to recombinant AAV's packaging cell line AE1201, which was exposed to Adenovirus 5 for two hours before transfection, we got rAAV/ACTK at the titer of 3.4 x 10(5) CFU/ml. After infecting human lung cancer cell A549 with rAAV/ACTK, we extracted host cell's chromosome cDNA and amplified part of the HSVI-TK sequence by a pair of HSVI-TK's primers and then hybridized to digoxin labelled HSVI-TK gene probe. We got corresponding positive band and it proved the integration of HSVI-TK into host cell's chromosome cDNA. By reverse transcripting rAAV/ACR-Neo infected A549 total cell RNA, we amplified part of HSVI-TK sequence and hybridized to Neo gene probe. The corresponding positive band demonstrated the expression of HSVI-TK. So through rAAV/ACTK, HSVI-TK was transferred into host cells and was expressed in them, the rAAV's genome was integrated into host cell's chromosome DNA. Connecting with Ganciclovir (GCV), the HSVI-TK gene transfer mediated by rAAV/ACTK, could inhibit the synthesis of chromosome DNA and lead to the killing of the lung cancer cell. This work proved that recombinant AAV could be used as vector for gene transduction to cancer cell, and also laid foundation for further research and application of AAV vector.

Cloning, Molecular↗
PubMed1995

Noise-enhanced performance in a cortical associative memory model.

Spontaneous neuronal activity and synaptic noise are well-known phenomena, but their biological significance has not yet been assessed. Using a computer model of the olfactory cortex we show that such activity, expressed as temporal noise in the model, can reduce recall time in associative memory tasks. We investigate both additive and multiplicative noise, and find optimal noise levels for which the recall time reaches a minimum. In addition, we demonstrate that noise can induce state transitions, such that the system is pushed from one attractor state to another. For high enough noise levels the dynamics can change dramatically and, for example, switch from an oscillatory to a chaos-like behavior. We discuss these findings in light of their significance for neural information processing.

Association Learning↗
PubMed1994

Using complexity measure to characterize information transmission of human brain cortex.

The information transmission among various parts of the cortex are computed with the theory of mutual information from the data of the electroencephalogram (EEG) time series of normal human subjects. The intensities of these transmissions are characterized by the "complexity" measures. These measures have revealed to be sensitively related to the functional conditions of human beings.

Adult↗
PubMed1994

[Changes in adhesion features of leukocytes in rats with severe burns].

Twenty-four rats were divided into 3 groups: normal controls (8), simple burned (8), burned plus Polygonum cuspidatum (p.c.)-treated (8). Three hours after burn, 3ml of whole blood was drawn to isolate polymorphonuclear neutrophilic leucocytes (PMNs). Confluent monolayer of rat microvessel endothelial cells was grown in a parallel plate of flow chamber. PMNs were driven through the flow chamber under different wall shear stresses. Leukocyte-endothelia adhesion was observed with an Olympus inverted microscope and recorded with a colour microscopic TV set. The adhesive characteristic curve of leukocyte was significantly different between the normal and burned groups. The number of PMNs adhesive to endothelium increased obviously 3 hours after burn. Under 0.196 Pa of wall shear stress, the adhesion rate of PMNs was 81.2 + 4.1% in the burned group and 58.8 + 4.6% in the normal group. The PNMs adhesion rate was decreased to near normal in p.c.-treated group. The average survival time in the burned group was 4.1 + 1.2 hours, much lower than that in the p.c. treated group (33.2 + 15.8 hours). However, in the simple burned group, one rat survived for 24 hours and its PMNs adhesive curve was similar to that of the normal or p.c.-treated groups. The findings indicate that PMNs adhesion features increase apparently after severe burn, which is closely related to the survival rate.

Animals↗
PubMed1993

Efflux of cyclic GMP from activated human platelets.

Activation of human platelets is associated with an increased level of cGMP, when total cGMP in individual samples is measured. However, by discriminating between intracellular and extracellular cGMP we were able to demonstrate that cGMP accumulates in the extracellular space only, whereas the level of intraplatelet cGMP actually decreases. Therefore, during the first minutes of platelet aggregation cGMP is released from the cell, and it thereby escapes hydrolysis by intracellular phosphodiesterases. In contrast, during direct activation of soluble guanylyl cyclase by nitrovasodilators, such as sodium nitroprusside, the newly synthesized cGMP remains mainly inside the cells. Elevation of intracellular calcium and activation of protein kinase C are likely to be involved in promoting cGMP efflux. Our results are discussed in contrast to the general hypothesis that the cGMP increase associated with platelet aggregation may represent a feedback mechanism designed to terminate early events of activating signal transduction. According to our data the apparent cGMP increase results from cGMP release from thrombocytes, rather than soluble guanylyl cyclase activation. This cGMP efflux provides a mechanism of decreasing the intracellular cGMP level upon stimulation with platelet agonists and thus favors platelet activation.

Blood Platelets↗
PubMed1992

Reversible activation of soluble guanylate cyclase by oxidizing agents.

Soluble guanylate cyclase of human platelets was stimulated by thiol oxidizing compounds like diamide and the reactive disulfide 4, 4'-dithiodipyridine. Activation followed a bell-shaped curve, revealing somewhat different optimum concentrations for each compound, although in both cases, higher concentrations were inhibitory. Diamide at a concentration of 100 microM transiently activated the enzyme. In the presence of moderate concentrations of diamide and 4,4'-dithiodipyridine, causing a two- to fourfold activation by themselves, the stimulatory activity of NO-releasing compounds like sodium nitroprusside was potentiated. In contrast, higher concentrations of thiol oxidizing compounds inhibited the NO-stimulated activation of soluble guanylate cyclase. Activation of guanylate cyclase was accompanied by a reduction in reduced glutathione and a concomitant formation of protein-bound glutathione (protein-SSG). Both compounds showed an activating potency as long as reduced glutathione remained, leading to inhibition of the enzyme just when all reduced glutathione was oxidized. Activation was reversible while reduced glutathione recovered and protein-SSG disappeared. We propose that diamide or reactive disulfides and other thiol oxidizing compounds inducing thiol-disulfide exchange activate soluble guanylate cyclase. In this respect partial oxidation is associated with enzyme activation, whereas massive oxidation results in loss of enzymatic activity. Physiologically, partial disulfide formation may amplify the signal toward NO as the endogenous activator of soluble guanylate cyclase.

Blood Platelets↗