Biomedical subjects

G Bi

Publications and source records attributed to G Bi.

13 recordsLinked to original sources

PubMed2001

Synaptic modification by correlated activity: Hebb's postulate revisited.

Correlated spiking of pre- and postsynaptic neurons can result in strengthening or weakening of synapses, depending on the temporal order of spiking. Recent findings indicate that there are narrow and cell type-specific temporal windows for such synaptic modification and that the generally accepted input- (or synapse-) specific rule for modification appears not to be strictly adhered to. Spike timing-dependent modifications, together with selective spread of synaptic changes, provide a set of cellular mechanisms that are likely to be important for the development and functioning of neural networks. When an axon of cell A is near enough to excite cell B or repeatedly or consistently takes part in firing it, some growth or metabolic change takes place in one or both cells such that A's efficiency, as one of the cells firing B, is increased.

Animals↗

PubMed2000

Selective presynaptic propagation of long-term potentiation in defined neural networks.

Induction of long-term potentiation (LTP) of the synaptic connection between two hippocampal glutamatergic neurons in a neural network formed in cell culture resulted in a specific pattern of potentiation at other connections within the network. We found that potentiation propagated from the site of induction retrogradely to glutamatergic or GABAergic synapses received by the dendrites of the presynaptic neuron and laterally to those made by its axonal collaterals onto other glutamatergic cells. In contrast, synapses made by the same presynaptic neuron onto GABAergic cells were not affected, and there was no postsynaptic lateral or forward propagation to other synapses received or made by the postsynaptic neuron. In addition, there was no secondary propagation to synapses not directly associated with the presynaptic neuron. Both induction and propagation of LTP required correlated spiking of the postsynaptic cell as well as the activation of the NMDA subtype of glutamate receptors. Such selective propagation suggests the existence of a long-range cytoplasmic signaling within the presynaptic neuron, leading to a specific pattern of coordinated potentiation along excitatory pathways in a neural network.

Animals↗

PubMed2000

[Germline LKB1 gene mutation screening in 4 Chinese Peutz-Jeghers syndrome pedigrees].

OBJECTIVE: To evaluate the frequency and nature of LKB1 gene germline mutations in 4 large Chinese Peutz-Jeghers syndrome pedigrees. METHODS: Four Chinese Peutz-Jeghers syndrome pedigrees were investigated. Two patients and 1 normal adult from each pedigree were selected, and genomic DNA from peripheral blood was extracted. The 9 exons of LKB1 gene were amplified by PCR. The products were tested by SSCP and abnormally shifted bands were sequenced. If there was no positive finding in any pedigree, the entire exons were sequenced. RESULTS: The same 842 C deletion of LKB1 gene frame-shift mutations was found in 2 pedigrees, which resulted in truncated protein. No exon variant was found in the left 2 pedigrees. CONCLUSIONS: LKB1 gene germline mutation is an important molecular pathogen of Peutz-Jeghers syndrome. 842 C deletion is a possible mutation hotspot and might be a common-ancestor mutation characteristic of Chinese.

AMP-Activated Protein Kinase Kinases↗

PubMed1999

Distributed synaptic modification in neural networks induced by patterned stimulation.

Activity-dependent changes in synaptic efficacy or connectivity are critical for the development, signal processing and learning and memory functions of the nervous system. Repetitive correlated spiking of pre- and postsynaptic neurons can induce a persistent increase or decrease in synaptic strength, depending on the timing of the pre- and postsynaptic excitation. Previous studies on such synaptic modifications have focused on synapses made by the stimulated neuron. Here we examine, in networks of cultured hippocampal neurons, whether and how localized stimulation can modify synapses that are remote from the stimulated neuron. We found that repetitive paired-pulse stimulation of a single neuron for brief periods induces persistent strengthening or weakening of specific polysynaptic pathways in a manner that depends on the interpulse interval. These changes can be accounted for by correlated pre- and postsynaptic excitation at distant synaptic sites, resulting from different transmission delays along separate pathways. Thus, through such a 'delay-line' mechanism, temporal information coded in the timing of individual spikes can be converted into and stored as spatially distributed patterns of persistent synaptic modifications in a neural network.

Animals↗

PubMed1999

[The rapid effects of steroids on glycine uptake in neuroblastoma cell strain SK-N-SH cells].

In the present study, glycine uptake in SK-N-SH cells was determined with liquid scintillation technique, and the rapid effects of steroids on glycine uptake in SK-N-SH cells were investigated. The results were as follows. High-affinity glycine uptake in SK-N-SH cells was dependent on Na+ and Cl-. Corticosterone (CORT), progesterone (P) and dexamethasone (DEX) had rapid effects on the glycine uptake. Since estradiol (E2) and deoxycorticosterone (DOC) had no effects, it was suggested that the rapid effects of steroids were specific. The rapid effects of CORT were concentration-dependent in a range of 10(-9)-10(-6) mol/L. The rapid effects were not affected by the inhibitor of protein synthesis and persisted even when CORT was conjugated with bovine serum album, but attenuated when Ca2+ was absent in the external medium. The results suggest that the steroid effect on glycine uptake in SK-N-SH cells was nongenomicly mediated.

Corticosterone↗

PubMed1996

Triplex formation by oligonucleotides containing novel deoxycytidine derivatives.

Homopurine sequences of duplex DNA are binding sites for triplex-forming oligodeoxyribopyrimidines. The interactions of synthetic duplex DNA targets with an oligodeoxyribopyrimidine containing N4-(6-amino-2-pyridinyl)deoxycytidine (1), a nucleoside designed to interact with a single C-G base pair interruption of the purine target tract, was studied by UV melting, circular dichroism spectroscopy and dimethylsulfate alkylation experiments. Nucleoside 1 supports stable triplex formation at pH 7.0 with formation of a 1-Y-Z triad, where Y-Z is a base pair in the homopurine tract of the target. Selective interaction was observed when Y-Z was C-G, although A-T and, to a lesser extent, T-A and G-C base pairs were also recognized. The circular dichroism spectra of the triplex having a 1-C-G triad were similar to those of a triplex having a C(+)-G-C triad, suggesting that the overall structures of the two triplexes are quite similar. Removal of the 6-amino group from 1 essentially eliminated triplex formation. Reaction of a triplex having the 1-C-G triad with dimethylsulfate resulted in a 50% reduction of methylation of the G residue of this triad. In contrast, the G of a similar triplex containing a U-C-G triad was not protected from methylation by dimethylsulfate. These results are consistent with a binding mode in which the 6-amino-2-pyridinyl group of 1 spans the major groove of the target duplex at the 1-C-G binding site and forms a hydrogen bond with the O6 of G. An additional stabilizing hydrogen bond could form between the N4 of the imino tautomer of 1 and the N4 amino group of C.

Alkylation↗

PubMed1996

Triplex formation by a psoralen-conjugated oligodeoxyribonucleotide containing the base analog 8-oxo-adenine.

Oligodeoxyribonucleotides containing thymidine and 8-oxo-2'-deoxyadenosine can form pyr.pur.pyr type triplexes with double-stranded DNA. Unlike triplexes whose third strands contain thymidine and deoxycytidine, the stability of these triplexes is independent of pH. We have prepared d-ps-TAAATAAATTTTTAT-L [I(A)], where A is 8-oxo-2'-deoxyadenosine, ps is 4'-hydroxymethyl-4,5',8- trimethylpsoralen and L is a 6-amino-2-(hydroxymethyl)hexyl linker. The oligomer is designed to interact with a homopurine sequence in the promoter region of the human gene coding for the 92 kDa form of collagenase type IV. Oligomer I(A) and oligomer I(C), which contains 2'-deoxycytidine in place of 8-oxo-2'-deoxycytidine, both form stable triplexes at pH 6.2, but only I(A) forms a stable triplex with a model duplex DNA target at pH 7.5, as determined by UV melting experiments. Triplex formation is stabilized by the presence of the psoralen group. Upon irradiation both I(A) and I(C) form photoadducts with the DNA target at pH 6.2, but only I(A) forms a photoadduct at pH 7.5. In these photoreactions oligomer I(A) appears to selectively form a photoadduct with a C in the purine-rich strand of the duplex target. Although a T residue is present in the pyrimidine-rich strand of the target at the duplex/triplex junction, essentially no adduct formation takes place with this strand, nor is interstrand cross-linking observed. The extent of photoadduct formation decreases with increasing temperature, behavior which is consistent with the UV melting curve of the triplex. A tetramethylrhodamine derivative of I(A) was prepared and found to cross-link less extensively than I(A) itself. Oligomer I(A) is completely resistant to hydrolysis when incubated for 24h in the presence of 10% fetal bovine serum at 37 degree C, although it is hydrolyzed by S1 nuclease. The properties of oligomer I(A) suggest that 8-oxo- containing oligomers may find utility as antigene oligonucleotide reagents.

Adenine↗

PubMed1994

Cell membrane resealing by a vesicular mechanism similar to neurotransmitter release.

After injury to the cell membrane, rapid resealing of the membrane occurs with little loss of intracellular contents. This process has been studied by measurement of the rate of dye loss after membrane puncture in both the sea urchin embryo and 3T3 fibroblasts. Resealing of disrupted cell membranes requires external calcium that can be antagonized by magnesium. Block of multifunctional calcium/calmodulin kinase, which regulates exocytotic vesicle availability at synapses, and of kinesin, which is required for outward-directed transport of vesicles, inhibited membrane resealing. Resealing was also inhibited by botulinum neurotoxins B and A, suggesting that the two synaptosomal-associated proteins synaptobrevin and SNAP-25 also participate in resealing. This pattern of inhibition indicates that the calcium-dependent mechanisms for cell membrane resealing may involve vesicle delivery, docking, and fusion, similar to the exocytosis of neurotransmitters.

3T3 Cells↗

PubMed1993

Heterokaryon myotubes with normal mouse and Duchenne nuclei exhibit sarcolemmal dystrophin staining and efficient intracellular free calcium control.

Duchenne and mdx muscle tissues lack dystrophin where it normally interacts with glycoproteins in the sarcolemma. Intracellular free calcium ([Ca2+]i) is elevated in Duchenne and mdx myotubes and is correlated with abnormally active calcium-specific leak channels in dystrophic myotubes. We fused Duchenne human and normal mouse myoblasts and identified heterokaryon myotubes by Hoechst 33342 staining to measure the degree to which dystrophin introduced by normal nuclei could incorporate throughout the myotube at the sarcolemma and restore normal calcium homeostasis. Dystrophin expression in myotubes was determined by immunofluorescence and confocal laser scanning microscopy. Dystrophin was expressed at the sarcolemma in normal mouse and heterokaryon myotubes, but not in Duchenne myotubes. In heterokaryons, extensive dystrophin localization occurred at the sarcolemma even where only Duchenne nuclei were present, indicating that dystrophin does not exhibit nuclear domains. Heterokaryon, normal mouse and Duchenne myotube [Ca2+]i was measured using fura-2 and fluorescence ratio imaging. Heterokaryon and normal mouse myotubes were found to maintain similar levels of [Ca2+]i. In contrast, Duchenne myotubes had significantly higher [Ca2+]i (p < 0.001). Furthermore, the ability of heterokaryons to maintain normal [Ca2+]i did not depend on greater numbers of normal nuclei than Duchenne being present in the myotube. These results support the view that dystrophin expression in heterokaryons allows for efficient control of [Ca2+]i.

Animals↗

PubMed1993

[Changes of angiotensin II contents in rat plasma, brain, cardiovascular system and adrenal during stress].

The changes of content of angiotensin II (A II) in plasma, anterior hypothalamus, medulla oblongata, myocardium, vasculature and adrenals during acute and chronic stress were studied in rats. Compulsive cold-water swimming and trauma by limb-breaking were used to set acute stress models while cold environment of 4-8 degrees C was used to set chronic stress model. The results showed that: (1) The A II levels in plasma were significantly increased in all three stress- model groups, reaching to 900%, 390% and 134% of the control in the swimming group, the limb-broken group and the cold environment group, respectively. It's clear that the level of angiotension II in the acute stress groups were much higher than those in the chronic stress group. (2) The A II levels of the rat brain, myocardium and blood vessel were also increased in the stress animals except the limb-broken group. Furthermore, the contents of angiotensin II of the chronic stress animals were significantly higher than those of the acute stress animals in the brain, myocardium and blood vessels, but not in the adrenals. (3) The adrenal A II content was significantly higher than that of the control in all stressed animals. (4) The plasma corticosterone was also significantly increased over the control level in both the acute and chronic stress groups. These results suggest that circulating angiotensin II and tissue angiotensin II may play a role during the development of acute and chronic stress, respectively.

Adrenal Glands↗

PubMed1991

[Morphine decreased the content of cyclic AMP in the rat spinal cord].

It has been reported that morphine or opiate-like substances (OLS) can affect the contents of cyclic AMP and/or cyclic GMP in mammalian brain, but very little is known whether similar effects also occur in spinal cord. Using RIA method, we showed that morphine significantly decreased the content of cyclic AMP in the rat spinal cord in vivo and in vitro and this effect could be completely blocked by naloxone, while the concentration of cyclic GMP in rat spinal cord is unchanged. In view of the present experiment it is suggested that the changes of cyclic AMP in the central nervous system may be partly mediated by the action of morphine.

Animals↗

PubMedDate not supplied

Expression of testis specific ankyrin repeat and SOCS box-containing 17 gene.

Human ASB-17 (Ankyrin Repeat and SOCS Box-containing 17) is a recently identified gene belonging to the ASB family, isolated from testis cDNA library. Human ASB-17 is expressed exclusively in testis among 16 tissues, revealed by Northern blot. Mouse Asb-17 was shown to be expressed from the third week post birth to adult by semi-quantitative RT-PCR analysis. In situ hybridization on frozen sections demonstrated that Asb-17 is expressed in spermatogenic cells in adult mouse, but not in Leydig cell and epididymis in adult mouse. ASB-17 proteins are highly conserved in mammals including human, mouse, rat, Canis familiaris and Macaca fascicularis.

Adaptor Proteins, Signal Transducing↗

PubMedDate not supplied

Changes in circulating and tissue angiotensin II during acute and chronic stress.

Changes of angiotensin II and cAMP in plasma, brain tissue, adrenal gland and cardiovascular tissue during the acute and chronic stress were studied in rats. The acute stress group was subjected to compulsive cold water swimming for 20 min, while the chronic stress group was exposed to an ambient temperature of 4-8 degrees C for 5 days. The results indicated that plasma angiotensin II levels were significantly increased in both stress groups, reaching up to 900% and 134% of the control in the acute and chronic groups, respectively. Angiotensin II contents in the anterior hypothalamus, medulla oblongata, myocardium, vasculature and adrenals were also elevated in both groups. With the exception of the adrenals, the contents of tissue angiotensin II in the chronic stress animals were significantly higher than those of the acute stress animals. In contrast, cAMP levels in plasma and tissue (hypothalamus and adrenals) and corticosterone levels in plasma in the acute stress group were all higher than those in the chronic stress animals, although the levels of the latter group were also increased compared with the control group. These results suggest that circulating and tissue angiotensin II may play an important role in the acute and chronic stress responses and that angiotensin II should be classified as a stress hormone.

Adrenal Glands↗