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Biomedical subjects

W Shan

Publications and source records attributed to W Shan.

At least 19 recordsLinked to original sources

Structure-based models of cadherin-mediated cell adhesion: the evolution continues.

Cadherins are glycoproteins that are responsible for homophilic, Ca2+-dependent cell-cell adhesion and play crucial roles in many cellular adhesion processes ranging from embryogenesis to the formation of neuronal circuits in the central nervous system. Many different experimental approaches have been used to unravel the molecular basis for cadherin-mediated adhesion. In particular, several high-resolution structures have provided models for cadherin-cadherin interactions that are illuminative in many respects yet contradictory in others. This review gives an overview of the structural studies of cadherins over the past decade while focusing on recent developments that reconcile some of the earlier findings.

Animals↗

Diluted II-VI oxide semiconductors with multiple band gaps.

We report the realization of a new mult-band-gap semiconductor. Zn(1-y)Mn(y)OxTe1-x alloys have been synthesized using the combination of oxygen ion implantation and pulsed laser melting. Incorporation of small quantities of isovalent oxygen leads to the formation of a narrow, oxygen-derived band of extended states located within the band gap of the Zn(1-y)Mn(y)Te host. When only 1.3% of Te atoms are replaced with oxygen in a Zn0.88Mn0.12Te crystal the resulting band structure consists of two direct band gaps with interband transitions at approximately 1.77 and 2.7 eV. This remarkable modification of the band structure is well described by the band anticrossing model. With multiple band gaps that fall within the solar energy spectrum, Zn(1-y)Mn(y)OxTe1-x is a material perfectly satisfying the conditions for single-junction photovoltaics with the potential for power conversion efficiencies surpassing 50%.

Journal Article↗

Therapeutic effects of astrocytes expressing both tyrosine hydroxylase and brain-derived neurotrophic factor on a rat model of Parkinson's disease.

Tyrosine hydroxylase (TH) and brain-derived neurotrophic factor (BDNF), expressed in normal astrocytes, were used in combination for the treatment of Parkinson's disease (PD) symptoms in a rat model. Normal neonatal rat astrocytes were co-transfected with a vector expressing BDNF (AAVBDNF) and a retroviral vector expressing TH (termed TH-BDNF-DA(+) cells), and then implanted into the striatum of PD rats induced by 6-hydroxydopamine. TH-BDNF-DA(+) cells compensated for a severe insufficiency of endogenous dopaminergic neurons in the PD rats, resulting in a significant improvement of PD symptoms. The decrease in the rotational rate of PD rats implanted with TH-BDNF-DA(+) cells was more marked than that in PD rats implanted with normal astrocytes expressing either TH or BDNF alone (termed TH(+) and BDNF(+) cells, P<0.01 and 0.001, respectively), and suggested a synergistic effect between TH and BDNF. In contrast, the rotational rate was not altered from the baseline in PD rats without treatment or implanted with parental rat astrocytes alone (P>0.05). BDNF protected the dopaminergic neurons from apoptosis induced by 6-hydroxydopamine, and significantly increased the long-term survival of TH-positive cells in the striatum. Our data indicate that the combined use of TH and BDNF has a synergistic therapeutic effect, and is more efficient for the treatment of PD than a single gene therapy using either TH or BDNF alone.

Animals↗

Stability of crystalline proteins.

By using two model proteins, glucose oxidase and lipase, we demonstrate that dry crystalline formulations are significantly more stable than their amorphous counterparts. The results of Fourier-transform infrared spectroscopy indicate that crystalline proteins better maintain their native conformation in accelerated stability studies. The lower tendency of crystalline proteins to aggregate is confirmed by size-exclusion chromatography. The data suggest that protein crystallization may significantly improve some aspects of protein handling, and change the way biopharmaceuticals are produced, formulated, and delivered.

Chromatography, Gel↗

Interaction of localized electronic states with the conduction band: band anticrossing in II-VI semiconductor ternaries

We report a strongly nonlinear pressure dependence of the band gaps and large downward shifts of the conduction band edges as functions of composition in ZnS xTe (1-x) and ZnSe (y)Te (1-y) alloys. The dependencies are explained by an interaction between localized A1 symmetry states of S or Se atoms and the extended states of the ZnTe matrix. These results, combined with previous studies of III-N-V materials define a new, broad class of semiconductor alloys in which the introduction of highly electronegative atoms leads to dramatic modifications of the conduction band structure. The modifications are well described by the recently introduced band anticrossing model.

Journal Article↗

Increasing numbers of synaptic puncta during late-phase LTP: N-cadherin is synthesized, recruited to synaptic sites, and required for potentiation.

It is an open question whether new synapses form during hippocampal LTP. Here, we show that late-phase LTP (L-LTP) is associated with a significant increase in numbers of synaptic puncta identified by synaptophysin and N-cadherin, an adhesion protein involved in synapse formation during development. During potentiation, protein levels of N-cadherin are significantly elevated and N-cadherin dimerization is enhanced. The increases in synaptic number and N-cadherin levels are dependent on cAMP-dependent protein kinase (PKA) and protein synthesis, both of which are also required for L-LTP. Blocking N-cadherin adhesion prevents the induction of L-LTP, but not the early-phase of LTP (E-LTP). Our data suggest that N-cadherin is synthesized during the induction of L-LTP and recruited to newly forming synapses. N-cadherin may play a critical role in L-LTP by holding nascent pre-and postsynaptic membranes in apposition, enabling incipient synapses to acquire function and contribute to potentiation.

Animals↗

Molecular modification of N-cadherin in response to synaptic activity.

The relationship between adhesive interactions across the synaptic cleft and synaptic function has remained elusive. At certain CNS synapses, pre- to postsynaptic adhesion is mediated at least in part by neural (N-) cadherin. Here, we demonstrate that upon depolarization of hippocampal neurons in culture by K+ treatment, or application of NMDA or alpha-latrotoxin, synaptic N-cadherin dimerizes and becomes markedly protease resistant. These properties are indices of strong, stable, enhanced cadherin-mediated intercellular adhesion. N-cadherin retained protease resistance for at least 2 hr after recovery, while other surface molecules, including other cadherins, were completely degraded. The acquisition of protease resistance and dimerization of N-cadherin is not dependent on new protein synthesis, nor is it accompanied by internalization of N-cadherin. By immunocytochemistry, we found that high K+ selectively induces surface dispersion of N-cadherin, which, after recovery, returns to synaptic puncta. N-cadherin dispersion under K+ treatment parallels the rapid expansion of the presynaptic membrane consequent to the massive vesicle fusion that occurs with this type of depolarization. In contrast, with NMDA application, N-cadherin does not disperse but does acquire enhanced protease resistance and dimerizes. Our data strongly suggest that synaptic adhesion is dynamically and locally controlled, and modulated by synaptic activity.

2-Amino-5-phosphonovalerate↗

[The relations between electrical synapse and the mechanism of epilepsy in genetical epilepsy-prone rat].

OBJECTIVE: To investigate the role of gap junction protein Cx32 formed electrical synapses in the pathogenesis of epilepsy. METHODS: Antisense oligodeoxynucleotides (ODN) techniques, intracerebroventricular injection, neuronal discharges in temporal cortex slices, in situ hybridization and immunohistochemistry were used. RESULTS: An antisense ODN for Cx32 100 micrograms was intracerebroventricularly injected once daily, for 3 days to P77PMC rat. The audiogenic seizure scores were significantly lowered as compared with the corresponding sense ODN (or PBS) treated control groups. Moreover, in the enterhinal cortex of the temporal cortex slice of antisense ODN treated P77PMC rat, the typical seizure like events and the late recurrent discharges were not induced by lower Mg2+ solution. The frequency and amplitude of neuronal discharges were decreased as compared with the control group. In situ hybridization and immunohistochemistry studies confirmed that Cx32 mRNA expression and Cx32 synthesis were also inhibited by Cx32 antisense ODN in P77PMC rat brain. CONCLUSION: Our results confirmed that gap junction formed electrical synapse between neurons plays an important role in the development of synchronization of neuronal discharges in vivo and in vitro.

Animals↗

Effects of antisense oligodeoxynucleotides to NR1 on suppression of seizures and protection of cortical neurons from excitotoxicity in vivo and in vitro.

OBJECTIVE: To investigate the effects of NR1 subunit on the initiation and development of seizures and protection of cortical neurons from excitotoxicity by using antisense oligodeoxynucleotides (ODN) to NR1 in vivo and in vitro. METHODS: Intracerebroventricular injection, temporal cortex slices discharge, cerebral cortical neuronal culture, induction of neurotoxicity and [3H]MK-801 binding were used in this study. RESULTS: After an antisense ODN for NR1 was administered intracerebroventricularly (i.c.v. 100 micrograms in 10 microliters) once daily, for three days in genetically epilepsy-prone rats (GEPR, P77PMC), the animals did not develop any clonic and tonic convulsions and their seizure scores were significantly lower compared to the control groups. The frequency and amplitude of early seizure-like events (SLEs) and late recurrent discharges (LRD), induced by lowering Mg2+, were reduced in entorhinal cortex (EC) of the temporal slice treated by antisense ODNs. Pretreatment with antisense ODN (2 microM) protected more than 52% of glutamate-sensitive neurons and reduced the [3H]MK-801 binding to 50% in cultured cerebral cortical neurons. CONCLUSIONS: N-methy-D-aspartate-receptors (NMDAR), specifically the NR1 subunit, may participate and play important roles in the initiation and propagation of epilepsy in the P77PMC rat.

Animals↗

[An antisense oligodeoxynucleotides for NR1 suppressed seizures and reduced discharges in the temporal cortex slice in genetically epilepsy-prone rat].

OBJECTIVE: To investigate the effects of N-methyl-D-aspartate receptors (NMDAR or NR) and NR1 subunit on mechanism of initiation and development epilepsy of genetically epilepsy-prone rat. METHODS: Antisense oligodeoxynucleotices (ODN) techniques, intracerebroventricular injection and experiments in vitro in rat temporal cortex slices were used. RESULTS: An antisense ODN for NR1, or the correspond sense ODN and normal saline was administered intracerebroventricular (i.c.v., 100 micrograms in 10 microliters) once daily, respectively for three days. P77PMC rats with antisense ODN did not display clonic and tonic convulsion, or showed that significantly lowered seizure scores compared to control groups. Moreover, the frequency and amplitude of early seizure-like events (SLEs) and late reccurrent discharges (LRDs), which induced by lowing Mg2+, were reduced in entorhinal cortex of the temporal cortex slice. CONCLUSION: Our results suggested that NMDA receptors, specifically the NR1 subunit, may participate in the initiation and development of epilepsy of P77PMC rat.

Animals↗

[A comparison of incidence of dental caries among primary and middle school pupils in Shanghai at 1982 and 1990].

In 1982 and 1990, two epidemiological surveys of dental caries of primary and middle school in Shanghai were carried out, using similar standards and methods. A comparison of the results revealed that: the incidence of caries of milk teeth continued to stay at a high level; the incidence of caries of permanent teeth showed a marked reduction. There was no difference between the two sexes. The incidence of caries of permanent teeth of the urban pupils is higher than that of the rural ones. Conversely, the incidence of caries of milk teeth of the rural pupils is still higher than that of the urban ones.

Adolescent↗

[Exploratory vitrectomy for traumatized eyes with no light perception and dense vitreous hemorrhage].

OBJECTIVE: To evaluate the efficacy of exploratory vitrectomy for certain traumatized eyes with no light perception (NLP) and dense vitreous hemorrhage. METHOD: We performed vitrectomy on 10 patients with NLP eyes after ocular trauma. Of them, eight had open globe injuries and two had closed blunt ocular trauma. RESULTS: Postoperatively, six had visual acuities of light perception to 0.25 and four remained NLP. In most eyes, a potentially functional posterior retina and optic disc were observed during surgery. CONCLUSION: Dense vitreous hemorrhage could be the most important factor for NLP after severe ocular trauma. Therefore, NLP does not always mean permanent loss of vision. Proper primary repair of the wound and timely vitrectomy may give a chance of visual recovery in selected traumatized eyes.

Adolescent↗

The human T-cell receptor TCRAC/TCRDC (C alpha/C delta) region: organization, sequence, and evolution of 97.6 kb of DNA.

We sequenced and analyzed 97.6 kb of new DNA sequence containing the human TCRAC (C alpha) and TCRDC (C delta) genes as well as the TCRDV3 (V delta 3) and 61 different TCRAJ (J alpha) gene segments and compared its organization and structure to the previously described mouse T-cell receptor TCRAC/TCRDC (C alpha/C delta) region. A comprehensive nomenclature, consistent with the IUIS nomenclature committee recommendations, for both human and mouse TCRAJ gene segments is presented. In the human sequence, we identified 20 new TCRAJ gene segments and obtained the germline sequence for 23 additional TCRAJ gene segments known from cDNA clones. Using the sequence data obtained from the human TCRAC/TCRDC region, we have extended a polymerase chain reaction-based assay to test for the expression of the individual TCRAJ gene segments. At least five TCRAJ pseudogene segments were identified by sequence criteria. Like the murine TCRAC/TCRDC sequence, this sequence contains a high level of coding sequence, with over 6.6% of the total sequence being transcribed. Comparison of the human sequence with the previously reported mouse DNA sequence reveals homologous counterparts for the variable and joining (J) gene segments and both constant genes. Eleven new J pseudogene segments have been identified in the mouse TCRAC/TCRDC sequence through the use of human and mouse sequence comparisons. In terms of structure and organization, this region of the human and mouse genome appears to be remarkably conserved.

Amino Acid Sequence↗